research and insights framework ccs

We've saved some files called cookies on your device. These cookies are:

• essential for the site to work
• to help improve our website by collecting and reporting information on how you use it

We would also like to save some cookies to help tailor communications.

• Search Contracts
• Search Buyers
• Help and Resources

Research & Insights Dynamic Purchasing System for Welsh Government Research Contracts

In 2021 Welsh Government encouraged key suppliers in the Research category, including all Universities, to apply for Crown Commercial Service’s (CCS) Research Marketplace.

  In 2021 Welsh Government encouraged key suppliers in the Research category, including all Universities, to apply for Crown Commercial Service’s (CCS) Research Marketplace – a Dynamic Purchasing System (DPS) providing research to public bodies across the UK.       

An 'open market' solution, a DPS is designed to give buyers access to a pool of pre-qualified suppliers, unlike a framework a DPS is an electronic system which suppliers can join at any time.

The existing DPS ends on the 15/02/2022 and a new Research & Insights DPS has been established and is live now. WG will continue to tender research requirements over the value of £25,000 through the new DPS and encourages current registered and interested suppliers to register.

All suppliers will need to register on the new Research & Insights DPS regardless of whether they are on the existing DPS.

Using the DPS provides numerous benefits including a ready-made platform for procuring research, reduction in time to procure for both the buying organisation and the supplier, opportunities for new suppliers to apply for the duration of the DPS and improved business intelligence. Suppliers will also have the opportunity to be invited for additional requirements across the wider Public Sector. The CCS Research DPS is a separate process to the Welsh Government Sell2Wales advertising process. When the Welsh Government use the CCS Research DPS, all tender information is advertised through the CCS DPS portal.  The WG will look to use the CCS DPS instead of tendering openly via sell2wales in the first instance. 

Applying for the DPS is a 7 stage process:

• Register on CCS Supplier Registration Service
• Register on the CCS eSourcing Tool to ensure you are invited to Calls for Competition- ensure you have selected the correct filters- you will only be informed of requirements for the filters selected
• Ensure the name and DUNS number on the CCS eSourcing tool matches your SRS registration and your DPS Selection Questionnaire (DPSQ) for RM6126
• Complete RM6126 DPSQ satisfying the DPS Selection Criteria.
• Supplier moves to “ Assessing ” stage – CCS compliance checks
• Supplier moves to “ Agreeing ” stage – Sign-off to complete appointment on the DPS
• Supplier moves to “ Appointed ” stage – Fully registered and able to bid in Calls for Competition.

CCS anticipate it takes up to one week to complete stages 1 to 4 and a further two to four weeks for stages 5 to 7. The CCS Bid Pack, Presentation and DPS Marketplace Instructions provides further detail of the process and CCS provide technical support at every stage through their support line 0845 299 2994 or an online contact form .

The new CCS Research & Insights DPS is live now and expires in December 2025, WG aim to procure research contracts over £25k via the DPS for the entire period that the DPS is live. We would encourage your organisation to apply for the DPS so you do not miss the opportunity to bid for our contracts.

Lines are open 8:30am to 5pm Monday to Friday.

Rydym yn croesawu galwadau'n Gymraeg.

We welcome calls in Welsh.

• Back to top
• About Sell2Wales
• How to use Sell2Wales
• Help and resources
• Privacy policy
• Terms & conditions
• Accessibility
• Open Contracting Transparency Data
• Welsh language policy

Research & Insights DPS

A tender notice by the minister for the cabinet office acting through crown commercial service.

• market and economic research
• crown commercial service
• insights dps
• research and development
• dps agreement
• period of validity of the dps
• provision of research
• increase capacity of high quality research

United Kingdom:

• Minister for the Cabinet Office Acting Through Crown Commercial Service Liverpool

Description

Crown Commercial Service (CCS) as the authority intends to put in place a DPS Agreement for the provision of Research and Insights services to be utilised by Central Government Departments and all other UK Public Sector Bodies, including local authorities, health, police, fire and rescue, education and devolved administrations and charities. It is intended that this DPS agreement will be the recommended vehicle for all research and behavioural insights services required by UK Central Government Departments.

Total Quantity or Scope

The RM6126 Research & Insights agreement will be organised into distinct categories so: ● bidders can indicate all elements relevant to their service offering ● customers can filter the elements to produce a shortlist of appointed suppliers to invite to a competition Crown Commercial Services (CCS) key priorities are to support visibility and control of research services whole life costs and to influence efficiencies through: ● offering valued research solutions to meet customers individual requirements ● build and increase capacity of high quality research and insights services outputs ● develop a dynamic commercial model for access to research and insights services The four (4) distinct categories comprise of: ● Subject area ● Research methods ● Target participants ● Research location Full details of the four (4) distinct categories and the sub-categories can be found at Annex A of the Buyer Needs document, and at DPS Schedule 1 (Specification) of the RM6126 Research & Insights DPS agreement terms and conditions, and also as Attachment 2 (Service Filter Matrix) in the bid pack. Additional information: Initial term of 48 months (4 years) CCS may extend the period of validity of the DPS for further two yearly periods at the end of the initial four year period and then at the end of each period of validity, as previously extended.

Renewal Options

CCS may extend the period of validity of the DPS for further two yearly periods at the end of the initial four year period and then at the end of each period of validity, as previously extended.

• 79300000 - Market and economic research; polling and statistics
• 73000000 - Research and development services and related consultancy services
• 73100000 - Research and experimental development services
• 73110000 - Research services
• 73111000 - Research laboratory services
• 73112000 - Marine research services
• 73200000 - Research and development consultancy services
• 73210000 - Research consultancy services
• 73300000 - Design and execution of research and development
• 73400000 - Research and Development services on security and defence materials
• 73430000 - Test and evaluation
• 79000000 - Business services: law, marketing, consulting, recruitment, printing and security
• 79310000 - Market research services
• 79311000 - Survey services
• 79311100 - Survey design services
• 79311200 - Survey conduction services
• 79311210 - Telephone survey services
• 79311300 - Survey analysis services
• 79311400 - Economic research services
• 79311410 - Economic impact assessment
• 79312000 - Market-testing services
• 79313000 - Performance review services
• 79314000 - Feasibility study
• 79315000 - Social research services
• 79320000 - Public-opinion polling services
• 79330000 - Statistical services
• 79340000 - Advertising and marketing services
• 79342310 - Customer survey services
• 79342311 - Customer satisfaction survey
• 79400000 - Business and management consultancy and related services
• 79410000 - Business and management consultancy services
• 79411000 - General management consultancy services
• 79411100 - Business development consultancy services
• 90711400 - Environmental Impact Assessment (EIA) services other than for construction
• This is a one-off contract (no recurrence)
• Renewals are available.
• Professional qualifications are sought.

Other Information

** PREVIEW NOTICE, please check Find a Tender for full details. ** The value provided in Section II.1.5) is only an estimate. The Authority cannot guarantee to suppliers any business through this DPS Agreement. The Authority expressly reserves the right: (i) not to award any DPS Agreement as a result of the procurement process commenced by publication of this notice; and (ii) to make whatever changes it may see fit to the content and structure of the tendering competition; and in no circumstances will the customer be liable for any costs incurred by the suppliers. (iii) to make changes to the management charge applicable to this DPS in relation to both the percentage charged and the methodology used. We consider that the Transfer of Undertakings (Protection of Employment) Regulations 2006 ("TUPE") may apply at the call for competition. It is the supplier’s responsibility to take your own advice and consider whether TUPE is likely to apply in the particular circumstances of the contract and to act accordingly. On 2.4.2014 Government introduced its Government Security Classifications (GSC) scheme which replaced Government Protective Marking Scheme (GPMS). A key aspect is the reduction in the number of security classifications used. All bidders should make themselves aware of the changes as it may impact on this requirement. The link below to Gov.uk provides information on the GSC at: https://www.gov.uk/government/publications/government-security-classifications . Cyber essentials is a mandatory requirement for central government contracts which involve handling personal information or provide certain ICT products/services. Government is taking steps to reduce the levels of cyber security risk in its supply chain through the cyber essentials scheme. The scheme defines a set of controls which, when implemented, will provide organisations with basic protection from the most prevalent forms of threat coming from the internet. To participate in this procurement, bidders must be able to demonstrate they comply with the technical requirements prescribed by cyber essentials, for services under and in connection with this procurement. Customers may enter into a contract with a supplier for a period of their determining which may exceed the RM6126 Research & Insights DPS, should this agreement be terminated at any time. The flexibility of the contracting period allows customers (Buyers) to determine appropriate contracting timelines required to enable the supplier to meet customer needs.

• ocds-h6vhtk-029a8d
• FTS 027493-2021
• contractsfinder.service.gov.uk
• crowncommercial.gov.uk
• youtube.com
• supplierregistration.cabinetoffice.gov.uk

• Distinguished Fellows
• Global CCS Foundation
• Opportunities
• Testimonials
• Case Studies
• Data & Knowledge
• CCS Strategy
• Advocacy & Communications
• CCS Database

Publications

• Insights and Commentaries
• Global Status of CCS 2023
• Previous Status Reports
• CCS Explained: Capture
• CCS Explained: Transport
• CCS Explained: Storage
• CCS Image Library
• Multimedia Library
• Institute Website – Japan
• Latest News
• CCS in the Americas
• Media Releases
• Members’ Portal
• Global Status of CCS 2022
• CCS Explained: The Basics

CCS Legal and Regulatory Indicator 2023

27th september 2023.

Read the Institute's thought leadership report titled "CCS Legal and Regulatory Indicator 2023" which offers an in-depth analysis of the legal and regulatory frameworks applicable to CCS in 56 jurisdictions.

Following the growing recognition of CCS as an essential climate mitigation solution, over the last two decades several jurisdictions around the world have implemented effective legal and regulatory regimes aimed at facilitating CCS activities and scaling up the technology. Developed by the Global CCS Institute, the CCS Legal and Regulatory Indicator (LRI) assesses the key factors needed to establish a comprehensive legal and regulatory framework for CCS.

Authored by the Institute’s Principal Consultant Policy, Legal and Regulatory, Ian Havercroft, and Consultant Legal and Regulatory, Nabeela Raji, this publication is the 3rd formal edition of the Institute's LRI, providing readers with detailed information, including:

• An updated snapshot of LRI scores from nations worldwide
• A clearly-defined methodology for undertaking a regular assessment, and comparisons of national legal and regulatory developments
• Key trends and issues influencing the development of CCS-specific law and regulation
• Progress of legal and regulatory developments, as well as gaps and opportunities, emerging across Europe, Middle East and Africa, Asia Pacific and the Americas

Back to Publications

The content within the Global CCS Institute Publications, Reports and Research Library is provided for information purposes only. We make every effort and take reasonable care to keep the content of this section up-to-date and error-free. However, we make no claim as to its accuracy, currency or reliability.

Content and material featured within this section of our website includes reports and research published by third parties. The content and material may include opinions and recommendations of third parties that do not reflect those held by the Global CCS Institute.

Get the latest CCS updates

The Workforce Development Trust listed on Crown Commercial Service Dynamic Purchasing System (DPS) for Research and Insights

The Workforce Development Trust has been added as an approved supplier to the Crown Commercial Service (CCS) DPS for Research and Insights.   

CCS is a government agency – part of the Cabinet Office – that supports the public sector to procure goods and services from trusted suppliers, ensuring value for money for the taxpayer.   

CCS frameworks and DPS’s cover a variety of categories, from Mobile Voice and Data Services to Facilities Management and Workplace Services, and contain a list of approved suppliers with whom terms and conditions and legal protections have been agreed.   

The Workforce Development Trust underwent a rigorous application process to be listed on the framework, which covers a variety of Research and Insights activities, including evidence based public service design and applied behavioural insights services.   

The Workforce Development Trust has been supporting public sector organisations through its Consultancy and Research division since 2002 and becoming a listed supplier on the CCS agreement for Research and Insights is reflective of the not-for-profit’s track record of service excellence.   

Jon Parry, Head of Research at The Workforce Development Trust, comments:   

“Our commitment as a charity is to provide industry leading consultancy and research services to support and empower public sector organisations deliver better frontline services.   

“Being a named supplier on the Research and Insights framework is a marker of quality and reflects the fact The Workforce Development Trust is regarded as a trusted partner of a variety of organisations across the public sector.”   

Cookies on GOV.UK

We use some essential cookies to make this website work.

We’d like to set additional cookies to understand how you use GOV.UK, remember your settings and improve government services.

We also use cookies set by other sites to help us deliver content from their services.

You have accepted additional cookies. You can change your cookie settings at any time.

You have rejected additional cookies. You can change your cookie settings at any time.

Record £2.8 billion commercial benefits delivered through Crown Commercial Service agreements

The newly published CCS annual report and accounts for 2021/22 shows £2.8 billion of commercial benefits were achieved across the public sector.

• Almost £3 billion achieved in commercial benefits in 2021/22 through CCS agreements
• Total spent through agreements has doubled over the past 5 years to £27.6 billion
• SMEs have benefited from £2.2 billion in direct spending, an additional £687 million directly compared to 2020/21

Almost £3 billion in commercial benefits have been achieved for public sector organisations through use of Crown Commercial Service (CCS) agreements, delivering record value for taxpayers.

CCS agreements provide public sector bodies with a choice of suppliers who offer the best value, leveraging the scale of public sector demand to secure competitive prices. By using these agreements, public sector customers can achieve commercial benefits such as reduced costs compared to market prices and better value in contract terms and conditions.

The newly published CCS annual report and accounts for 2021/22 shows £2.8 billion of commercial benefits were achieved across the public sector. CCS agreements secured £1.9 billion in benefits for central government, and a further £0.9 billion for the wider public sector.

This includes £4 million in savings for 14 NHS trusts on mobile and data services, such as voice calls, connectivity and applications. The Student Loan Company also saved £1.6 million by outsourcing its print and mail services through CCS’s Managed Print and Digital Solutions framework.

ACRO Criminal Records Office, a national police unit, was able to improve efficiency and accuracy by putting in place a machine translation solution through CCS’s Language Services framework. This enabled the organisation to translate vital conviction information quickly from EU member states and prevent criminal cases being thrown out of court, saving £6,000 in 3 months and helping to make our streets safer.

Minister for Brexit Opportunities and Government Efficiency, Jacob Rees-Mogg said:

The Crown Commercial Service is one of the highest-performing parts of the Government. It provides the best value for taxpayers day in, day out. At a time of high inflation and squeezed budgets, its work is more valuable than ever. By leveraging the scale of public sector demand when choosing suppliers, these agreements have secured billions in savings, which can be used to support vital services delivered across the public sector.

Spending through CCS frameworks has doubled in five years, reaching £27.6 billion in 2021/22. This means CCS is on course to hit its target of £30 billion by 2024 and represents an increase of £4.9 billion on the 2020/21 total. CCS also assisted customers with contracts valued at over £5 billion annually by running procurements on their behalf.

The amount spent directly with small and medium-sized businesses (SMEs) increased by £687 million compared to the year before. In total, £2.2 billion was spent directly with SMEs, supporting growth and jobs across the UK.

Simon Tse, CEO of Crown Commercial Service, said:

Growing the economy is a top priority and supporting small businesses will do just that. The past year has seen record spending with SMEs through CCS agreements and suppliers have been paid promptly, aiding their growth and spreading economic prosperity across the country.

CCS agreements have also supported public sector customers with key policy priorities, such as net zero commitments and supply chain auditing.

Thousands of customers used CCS’s dedicated net zero web pages over the last 12 months to identify agreements that help them meet sustainability goals.

CCS also published its first annual modern slavery statement in November. This set out steps being taken to identify, prevent and mitigate the risks of modern slavery in CCS operations and supply chains, including ensuring that suppliers are publishing an annually updated modern slavery statement.

Chair of the CCS Board, Tony van Kralingen said:

Crown Commercial Service has once again driven significant value for taxpayers, while continuing to develop and enhance its reputation for excellence across central government and the wider public sector. I am delighted to be able to end my term as Chair of the CCS Board with such outstanding results. The Board and I are confident that the platform for continued success is well established.

The year at a glance

• £27.6 billion of public sector spend was channelled through CCS agreements, doubling spend over 5 years
• Customers who have used CCS agreements have achieved commercial benefits equivalent to £2.8 billion
• CCS’s employee engagement index, as measured by the Civil Service People Survey, remains high at 71% in 2021
• £2.2 billion was spent directly with SMEs through CCS’s commercial agreements in 2021/22 - an additional £687m compared to 2020/21
• The assisted procurement service helped deliver procurements for customers worth a total annual contract value of £5 billion

Read the full report

You can read CCS’s Annual Report and Accounts .

You can find a full list of all the commercial agreements CCS offers, alongside details of how CCS can help you build policy considerations into your procurement, in our interactive digital brochure .

Share this page

The following links open in a new tab

• Share on Facebook (opens in new tab)
• Share on Twitter (opens in new tab)

Updates to this page

Is this page useful.

• Yes this page is useful
• No this page is not useful

Help us improve GOV.UK

Don’t include personal or financial information like your National Insurance number or credit card details.

To help us improve GOV.UK, we’d like to know more about your visit today. Please fill in this survey (opens in a new tab) .

Procurement routes

Easy ways to buy our services, approved frameworks, g-cloud frameworks, dos frameworks, nhs frameworks, ccs print frameworks, scottish frameworks, joscar registered, ccs dps ai and automation frameworks, ccs research & insights, ccs communications marketplace, approved g-cloud supplier on the digital marketplace.

We are an approved G-Cloud supplier, having been awarded the framework contract by the Government Procurement Service.

G-Cloud is a UK Government Programme to encourage the adoption of Cloud Services across the whole of the Public Sector.

G-Cloud provides a marketplace of pay-as-you-go commodity services that can be scaled up or down, based on the changing needs of a business and its users.

We offer a range of public-sector specific cloud-based solutions via the Digital Marketplace, as well as cloud hosting and a full range of related support services.

We are currently on:

• G-Cloud 13 (RM1557.13)

On G-Cloud13, we offer the following services:

Cloud Hosting

• Azure cloud hosting
• AWS cloud hosting
• UKCloud cloud hosting

Cloud Software

• Optimizely content cloud DXP
• Umbraco managed cloud platform
• Appian cloud solutions
• MicroStrategy cloud
• Panintelligence business intelligence
• Brandworkz brand management software
• Sisense managed cloud

Cloud Support

• Accessibility consultancy and audit services
• Application consultancy, development and support services
• Business process management and transformation consultancy and implementation
• Case management cloud solutions
• Cloud security and monitoring services
• CMS solution consultancy, implementation and support
• Content production cloud solutions
• Content strategy and design consultancy
• Cyber and information assurance consultancy
• Data architecture, analysis, and consultancy
• Digital experience platforms (DXP)
• Digital experience platform (DXP) design and performance
• Digital services consultancy
• Hybrid mail and outbound communications
• Hyperautomation
• Inclusivity consultancy, user testing and research services
• Insight and content services
• Internal communications solution consultancy
• Low-code solution implementation and support
• Management information and business intelligence consultancy services
• MicroStrategy BI consultancy, design, implementation, and support
• Process automation cloud solutions
• Property asset management consultancy, design, implementation, and support
• Public access solution consultancy
• Secure by design technical consultancy
• Secure infrastructure and monitoring design
• Service design, user centred design, and UX consultancy
• Splunk consultancy, implementation, and support

UK Government DOS framework supplier

CDS are on the UK Government’s Digital Outcomes and Specialists (DOS) Framework. We have been on the DOS Framework since April 2016.

Our services and people are available via:

• Lot 1: Digital Outcomes
• Lot 2: User Research Studios
• Lot 3: User Research Participants

The DOS Framework replaced the Digital Services Framework and aims to make it simpler, clearer and faster for those in the public sector to buy what they need from approved suppliers.

Public sector organisations can use the framework, found on the Digital Marketplace, to find specialists to help them deliver digital projects, or suppliers to deliver a combination of services for a particular outcome. CDS are ready to help you shape your digital transformation journey. Take advantage of our industry-leading knowledge and proven track record in delivering digital services for the public and private sectors.

• DOS 6 (RM1043.8)

NHS print specialists

We are on two of the largest NHS frameworks. CDS was awarded a place on the NHS London Procurement Partnership (NHS LPP) Clinical and Digital Information Systems Framework (CDIS).

Talk to an NHS print procurement specialist and see how we can help successfully deliver your next project.

We were awarded a place on the following lots:

• 3.2: Hybrid mail and related communication services
• 3.3: External print and related services

We are a HealthTrust Europe GPO framework supplier. HealthTrust Europe is a Group Purchasing Organisation (GPO) who are committed to strengthening provider performance and clinical excellence in healthcare.

HealthTrust Europe supports the delivery of high-quality, cost-effective care in the communities they serve.

Information Management and Technology (IM&T) framework

We are also on the NHS London Procurement Partnership framework. This framework is available to all NHS trusts and the wider public sector.

We are on the following:

• Lot 4 Software/Sub-Lot 4.5 Informatics & Reporting (CDS and Microstrategy)
• Lot 4 Software/Sub-Lot 4.6 Customer Service/Call Centre CRM basket (CDS and Appian)

Public sector print 1 management solutions - CCS RM6170 Framework

We are excited to announce that we have secured a place on the new Crown Commercial Service print management solutions framework which went live 28 December 2020 replacing the expired print and digital solutions framework RM3785 which terminated 27 December 2020.

CDS are one of six key suppliers on Lot 2 of the new framework which is open to the Public Sector and Wider Public Sector. Both Lots 1 and 2 offer similar services but the advantage of Lot 2 is that a mini-competition is undertaken by the buyer involving all six suppliers whereas Lot 1 is a direct award without competition to a single supplier. Lot 2 enables a bespoke, tailored print management solution based on the precise requirements and is a popular route to market.

Services available are extensive and cover a full range of Print Services including, Pre-production; project and account management; print production (all formats); bulk print; direct mail and transactional print; digital asset management, a full range of finishing services; storage, fulfilment and distribution; digital and transformation services and specialist print services including electoral print.

Benefits of the CCS RM6170 Framework – Lot 2:

• Significant savings using a transparent price model
• Access to a full managed print and digital solution, which is fully compliant
• Efficient and easily accessed after a short procurement process involving a mini-competition
• Pre-agreed terms and conditions offer contractual safeguards
• Conducting independent procurement would take far longer and cost more
• All approved suppliers were scrutinised and formally evaluated by the CCS Team
• Approved suppliers have invested in key management systems which include: Cyber Essential PLUS, Business Continuity, Environment, Health and Safety, Data Management Systems and Data Protection
• Lot 2 assures your organisation will achieve savings and benefit from excellent account management, help, advice, product engineering and consultancy.

Postal Goods, Services and Solutions - CCS RM6017 Framework 

We offer a wide range of postal goods, services and solutions to support your postal requirements and strategy, no matter where you are in that journey.

Whether you use traditional mail services or would like to transform your mailroom to digital, we can help. You will have access to traditional postal goods and services such as security screening, franking machines, mailroom equipment, collection and delivery services for UK and international mail.

The agreement also offers audits, efficiency reviews and consultancy services to help you develop your postal services strategy. A range of inbound and outbound services are available to transition from a paper-based mailroom to a digital environment.

This includes hybrid mail solutions that incorporate new technologies and innovation, such as e-communications and fully outsourced, innovative managed service options, for a ‘digital by default’ paper-lite strategy.

Public Contracts Scotland

The Public Contracts Scotland portal was launched in August 2008 to provide a national advertising website for Scottish public bodies to post higher value regulated procurements, lower-value notices, and subsequent contract awards; prime contractors on public sector contracts can also advertise sub-contract opportunities.

We are on the Digital Technology and Cyber Services (DTCS) framework for Lot 1 - Digital Technology Projects and Services.

RM6200 Artificial Intelligence (AI) and RM6173 Automation

We are now included on the CCS DPS frameworks for Artificial Intelligence and Automation .

I f you are new to AI or automation, CDS will help you build your case for investment, understand the AI and automation landscape, advise on best practice, run and manage your discovery process, and engineer your solution. The great news is that you can now use the Artificial Intelligence and Automation Marketplace DPS ’ to commission projects and start your business transformation journey with confidence.

CCS RM6126 Research & Insights 

We are included on the CCS RM6126 Research and Insights framework .

We believe in creating successful, human-centred solutions by helping you understand your audience.

Our approach to research includes all members of your audience—users of different ethnicities, age groups, and hard-to-reach users with varying access needs—to ensure your solutions are inclusive.

Learn from user experiences and uncover issues, opinions, and needs to shape business decisions, create informed policies, and develop knowledge that will help improve your products or services.

With help from our accessibility experts, produce a solution that is accessible to all and meets regulatory requirements. 

CCS RM6124 Communications Marketplace

We are included on the CCS RM6124 Communications Marketplace Framework . 

Run successful public service campaigns with more sophisticated targeting of your audience. Through specialist marketing and communications services, we can help you utilise your data, design creative content, provide strategy, consultation, and production, and more, to ensure that your communications are clear, engaging, and effective.

Our Credentials

Celebrated, tested and trusted.

Obviously, we can’t help but be proud when the positive differences we’ve made get a big thumbs-up from our peers. 

Certifications

These aren’t just tick-box exercises for us. They shape how we work and act at all times.

• Sustainability
• Client Login

• Built Environment
• Energy & Natural Resources
• Financial Services
• Government & Public Sector
• Technology, Media & Communications

Legal Services

• Commercial, Regulatory & Data
• Dispute Resolution
• Employment and Pensions
• Finance and Restructuring
• Real Estate
• Tax & Private Capital
• India Group

Legal Operations

• Contracts Management
• Cyber Incident Services
• Legal Analytics
• Legal Operations & Consulting
• Litigation and Investigations

Business Services

• Claims Management & Adjusting
• Corporate Governance & Compliance
• DWF Chambers
• Regulatory Consulting
• Class Actions
• Economic Crime & Fraud Hub
• Sustainable Business & ESG
• Data Protection and Cyber Security
• News and Insights
• Reports and Publications
• News and Press
• Brave New Law
• DWF Link: Business leaders of the future
• Consumer Duty Hub
• Press Releases
• DWF appointed across CCS framework

DWF appointed across all lots of Crown Commercial Service framework for Wider Public Sector Legal Services

DWF, the global provider of integrated legal and business services, has been named as a supplier on the Crown Commercial Service framework for Wider Public Sector – Legal Services.

DWF's appointment spans all three lots, giving the business the ability to advise the wider public sector, primarily local government and other associated bodies, through the panel, across England, Wales, Scotland and Northern Ireland as well as through a separate transport and rail lot. 

DWF was on the previous version of this panel across several lots, but has secured a greater number of lots this time. 

This follows on from the news in December 2021  that DWF was successful in being appointed to the UK Government's Crown Commercial Service's (CCS) Legal Services Panel, to provide general legal services to UK central government departments and other public sector bodies.  Crown Commercial Service supports the public sector to achieve maximum commercial value when procuring common goods and services. In 2021/22, CCS helped the public sector to achieve commercial benefits equal to £2.8 billion - supporting world-class public services that offer best value for taxpayers. Jonathan Branton , Partner and Head of Government and Public Sector at DWF, said:  "We are delighted to have been appointed to the new panel across all lots. Having a place on both the local and central government panels enables us to help solve complex legal issues right across the public sector and it is another indication of our leading reputation in the sector."

Related Authors

Press Office

Related sectors.

• Government & Public Sector
• Regional & Local Government

Further Reading

India’s 2024 budget, presented by Finance Minister Nirmala Sitharaman, marks a significant shift in the government’s priorities, focusing on rural development, job creation, and agriculture. We summarise our key highlights and the key considerations for the legal sector:

DWF, the global provider of integrated legal and business services, is delighted to announce the appointment of Rebecca McMahon as DWF's first dedicated Pro Bono and Community Special Counsel. 

Research and advice

CCS Insight / Services / Research and advice

Insights for informed decisions.

We deliver market insight in a variety of ways, all tailored to the needs of our clients, whether you’re looking for facts and figures from market surveys or line-by-line commentary in our written reports.

All of our market-leading content is delivered through the filter of our highly knowledgeable analyst team, who bring additional depth to data through the value of their personal touch.

And the quality of our content is matched by the targeted nature of our delivery. We listen and respond, maintaining open communication to ensure clients access the level of insight they need.

CCS Insight Connect

The backbone of our data offering, Connect provides CCS Insight clients with access to an ever-expanding pool of high-value market information and analysis. 

Find out more about CCS Insight Connect .

Explore further

Marketing services

Spotlight: Direct Satellite-to-Device Mobile Services

Please fill in your details below and click submit to request your download.

" * " indicates required fields

Get in touch

Our global team of analysts understand what clients need and are ready to provide it.

We're great to work with. You'll be glad we're on your side.

You can call us for a quick opinion and we'll respond.

Subscribe to our blog

• Open access
• Published: 31 August 2024

Employing a synergistic bioinformatics and machine learning framework to elucidate biomarkers associating asthma with pyrimidine metabolism genes

• Dihui Zhang 1   na1 ,
• Xiaowei Pu 2   na1 ,
• Man Zheng 3 ,
• Guanghui Li 3 &
• Jia Chen 2  

Respiratory Research volume  25 , Article number:  327 ( 2024 ) Cite this article

Metrics details

Asthma, a prevalent chronic inflammatory disorder, is shaped by a multifaceted interplay between genetic susceptibilities and environmental exposures. Despite strides in deciphering its pathophysiological landscape, the intricate molecular underpinnings of asthma remain elusive. The focus has increasingly shifted toward the metabolic aberrations accompanying asthma, particularly within the domain of pyrimidine metabolism (PyM)—a critical pathway in nucleotide synthesis and degradation. While the therapeutic relevance of PyM has been recognized across various diseases, its specific contributions to asthma pathology are yet underexplored. This study employs sophisticated bioinformatics approaches to delineate and confirm the involvement of PyM genes (PyMGs) in asthma, aiming to bridge this significant gap in knowledge.

Employing cutting-edge bioinformatics techniques, this research aimed to elucidate the role of PyMGs in asthma. We conducted a detailed examination of 31 PyMGs to assess their differential expression. Through Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), we explored the biological functions and pathways linked to these genes. We utilized Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) to pinpoint critical hub genes and to ascertain the diagnostic accuracy of eight PyMGs in distinguishing asthma, complemented by an extensive correlation study with the clinical features of the disease. Validation of the gene expressions was performed using datasets GSE76262 and GSE147878.

Our analyses revealed that eleven PyMGs—DHODH, UMPS, NME7, NME1, POLR2B, POLR3B, POLR1C, POLE, ENPP3, RRM2B, TK2—are significantly associated with asthma. These genes play crucial roles in essential biological processes such as RNA splicing, anatomical structure maintenance, and metabolic processes involving purine compounds.

Conclusions

This investigation identifies eleven PyMGs at the core of asthma's pathogenesis, establishing them as potential biomarkers for this disease. Our findings enhance the understanding of asthma’s molecular mechanisms and open new avenues for improving diagnostics, monitoring, and progression evaluation. By providing new insights into non-cancerous pathologies, our work introduces a novel perspective and sets the stage for further studies in this field.

Introduction

Asthma, a chronic and complex disease, affects over 300 million individuals globally, with projections suggesting an increase to 400 million by 2025 [ 1 ]. Characterized by pervasive airway inflammation and intricate cellular dynamics, asthma presents significant global health challenges, as indicated by the Global Asthma Network (GAN) with prevalence rates of 10.5% among children and 4.4% among adults [ 2 ]. The disease manifests through symptoms such as airway hyperresponsiveness, eosinophilic infiltration, reversible airflow obstruction, airway remodeling, mucus hypersecretion, and goblet cell hyperplasia [ 3 ]. Despite extensive research, the underlying mechanisms of asthma remain poorly understood, a consequence of its multifactorial nature involving genetic, environmental, infectious, immunological, and dietary components. Current therapeutic approaches primarily target symptom control, often leaving a considerable number of patients undermanaged [ 4 ]. This gap underscores the critical need for an in-depth investigation into the genetic and molecular bases of asthma, which could revolutionize our understanding of its onset and progression [ 5 ]. Advancements in this field promise to shift from merely managing symptoms to altering the disease trajectory, potentially transforming asthma treatment and significantly enhancing patient care worldwide [ 6 ].

PyM plays a pivotal role in the synthesis, degradation, and recycling of critical pyrimidine nucleobases, such as cytosine and uracil, which are crucial to nucleic acid structures. Beyond its foundational role in nucleic acid synthesis, PyM is intricately linked to broader aspects of energy metabolism through its biosynthetic and catabolic pathways, encompassing both de novo and salvage routes [ 7 ]. These pathways are particularly vital in rapidly dividing cells [ 8 ]. Disruptions in PyM pathways can lead to a range of inherited metabolic and autoimmune inflammatory disorders, including asthma. Recent studies highlight the role of microRNAs, notably miR-146a and miR-155, in promoting asthma by downregulating genes that typically suppress cell proliferation [ 9 ]. Furthermore, modulation of these microRNAs through TSHR-mediated pathways reveals insights into the fibroproliferative characteristics of asthma. Research by Madera-Salcedo et al. has shown that inflammation-induced hypermethylation of PPP2R2B (B55ß) leads to resistance to apoptosis in the absence of cytokines [ 10 ]. Concurrently, Zhu et al. demonstrated how UBE2T exacerbates the progression of hepatocellular carcinoma by influencing PyM [ 11 ]. This research aims to dissect the role of PyMGs in asthma immunotherapy, seeking to uncover new therapeutic opportunities by investigating purinosome formation and the glutamine pyrimidine metabolism pathway [ 12 ]. Despite significant progress, the impact of PyM on the immunogenic landscape and its critical role in enhancing the efficacy of immunotherapies for asthma remain poorly understood. This study is committed to a comprehensive assessment of PyMGs and their integration with immunotherapeutic strategies in asthma, potentially leading to transformative clinical advancements.

The Asthma Initiative heralds a transformative leap in biomedical research, integrating comprehensive transcriptomic sequencing with detailed clinical annotations to elucidate the transcriptional and molecular intricacies of asthma [ 13 , 14 , 15 ]. This project employs cutting-edge bioinformatics to navigate vast datasets, aiming to unveil the complex pathophysiological foundations of the disease. Notably, the role of PyMGs in the asthma schema remains underexplored. Our study addresses this oversight by utilizing asthma-specific datasets from the GEO to investigate the impact and relevance of PyMGs on asthma pathogenesis, as illustrated in Fig.  1 . Through this focused analysis, we aim to enhance our understanding of asthma’s molecular basis and pave the way for novel therapeutic strategies.

Materials and methods

The methodologies proposed by Zi-Xuan Wu et al. in 2023 were employed in this study [ 16 ].

GEO was searched for mRNA expression. Series: GSE76262 and GSE147878. Platform: GPL13158 and GPL6480. Strategy for searching (‘Parkinson’ [MeSH] mRNA [All Fields] and normal) AND (‘Homo sapiens’ [Organism] AND ‘Non-coding RNA profiling by array’ [Filter]). Specifically, this investigation harnessed the datasets GSE76262 and GSE147878, underpinned by the GPL13158 and GPL6480 platform. GSE76262 functioned as the training cohort, while GSE147878 constituted the testing group (Table  1 ). We also identified PyMGs from the MSigDB (Table S1).

Analysis of differentially expressed genes (DEGs)

Our methodology for extracting precise mRNA profiles involved the utilization of Perl scripts to meticulously match and sort transcriptional data from the GSE76262 dataset. Following normalization procedures, we applied stringent criteria for identifying differential expression among PyMGs: FDR < 0.05 and |log2FC|≥ 1. This rigorous approach enabled the isolation of significantly altered PyMGs for further scrutiny. To elucidate the intricate relationships among these genes, Pearson's correlation coefficient was harnessed, leveraging the corrplot package in R for comprehensive correlation analysis. This step was pivotal in highlighting genes with statistically significant associations within the identified modules.

GO and KEGG analysis

To elucidate the biological implications and pathway involvements of the differentially expressed genes (DEGs), we conducted comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Employing the R programming language, we investigated the impact of differentially expressed PyMGs on biological processes (BP), molecular functions (MF), and cellular components (CC). This analysis aimed to delineate the overarching biological themes and molecular pathways influenced by these genes, thereby enhancing our understanding of their roles in disease pathology and identifying potential therapeutic targets. Through this multi-faceted approach, we not only categorized the DEGs but also shed light on the intricate interplay between purine metabolism and its broader biological and clinical significance.

Model construction and analysis of immune cell infiltration

In our pursuit of a predictive model characterized by unparalleled precision and reliability, we utilized the glmnet package for Lasso regression analysis, complemented by cross-validation, to refine and enhance our model. This methodology effectively mitigated overfitting, thereby boosting the model's predictive capability for complex biological datasets. For further validation, we employed the sophisticated SVM-RFE algorithm using the e1071 package, meticulously constructing a machine learning model. Cross-validation was pivotal in assessing the model's error rates and accuracy, ensuring its robustness and dependability. The Random Forest algorithm, renowned for its efficacy in ensemble learning, was integral to our analysis. By generating multiple decision trees and aggregating their predictions, it minimized overfitting risks and enhanced model generalization. The algorithm's distinctive feature—random feature selection and bootstrap sampling—fostered diversity among decision trees, thus improving the model's overall accuracy. Utilizing the randomForest and ggplot2 packages, we concentrated on analyzing differentially expressed genes, identifying key genes crucial for disease classification. In the final phase, we ranked the significance of these feature genes using an integrated approach that synthesized insights from Lasso regression, Random Forest, and SVM models. This provided a nuanced understanding of their roles in disease pathology. Furthermore, the CIBERSORT algorithm enabled us to analyze the immune cell composition, offering deeper insights into the immune landscape associated with the disease. This comprehensive and rigorous analytical approach not only augmented the accuracy of disease classification but also unveiled new avenues for understanding the molecular basis of the disease.

GSEA and GSVA

To elucidate the functional dynamics and pathway alterations across a spectrum of samples, we employed Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). These powerful methodologies enabled the identification of functionally related gene sets and pathway changes, utilizing quantitative scores and visual representations to highlight active biological processes and pathways within various risk stratifications. Using R, we thoroughly investigated the impact of differentially expressed PyMGs on BP, MF, CC, and pathways, providing a granular understanding of their roles in disease mechanisms. This approach allowed us to uncover the intricate biological themes and molecular pathways influenced by these genes, thereby enhancing our comprehension of their involvement in disease pathology.

Drug-gene interactions in asthma

As bioinformatics in asthma research progresses towards pinpointing viable biomarkers, the construction of biological models and the identification of effective markers for disease diagnostics have become increasingly critical. Grasping the clinical relevance of these biomarkers is essential for crafting targeted therapeutic approaches. Anticipating drug reactions based on these pivotal markers is fundamental for the development of future preventative measures and therapeutic regimens for asthma. In this vein, validated biomarkers stand as crucial reference points. Thus, precise prediction of drug-gene interactions holds paramount significance. In this study, the Drug-Gene Interaction database (DGIdb) ( https://dgidb.genome.wustl.edu/ ) was utilized to forecast interactions between the identified hub genes and prospective therapeutic agents, highlighting the potential for targeted intervention strategies in asthma management.

Investigation of shared miRNAs and lncRNAs in asthma

The regulatory landscape of genetics is profoundly influenced by non-coding RNA transcripts, particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). miRNAs modulate gene expression by enhancing or repressing mRNA degradation and translation, while lncRNAs, consisting of over 200 nucleotides, orchestrate a multitude of cellular processes through mechanisms such as chromosomal modifications, transcriptional activation, and interference. Recent studies have illuminated the extensive interplay between miRNAs and lncRNAs, fostering a competitive binding scenario among miRNAs, lncRNAs, and other regulatory entities. This interaction has led to the concept of competitive endogenous RNAs (ceRNAs), where lncRNAs can regulate gene expression by sequestering miRNAs. In light of these findings, our investigation aims to determine whether specific miRNAs and lncRNAs share regulatory mechanisms and developmental pathways in Asthma, potentially unveiling novel avenues for understanding and treating this complex condition.

Establishment of a common mRNA-miRNA-lncRNA network in asthma

To elucidate the interactive landscape among mRNA, miRNA, and lncRNA entities in Asthma, we sourced target gene information from miRTarBase and PrognoScan, databases renowned for providing empirically validated miRNA-lncRNA-target interactions. By intersecting the target genes of common mRNA-miRNA-lncRNA interactions with Asthma-associated genes, we established a regulated network. This network was visualized using Cytoscape software, providing a graphical representation of the molecular interplay critical to Asthma pathophysiology.

Mendelian randomization analysis

To ensure the independence of exposure and outcome variables in our genome-wide association study (GWAS) summary data, we engaged in an association analysis via the TwoSampleMR package in R. Designating NME7 and POLR2B-related expression as the exposure and Asthma as the outcome, we aimed to explore potential causal relationships. The analysis entailed: 1. Instrumental Variables (IVs) Configuration: NME7 and POLR2B-related expressions were screened with a P-value threshold of < 5 × 10^-8 to identify strongly associated exposures. 2. Independence Configuration: Linkage disequilibrium (LD) between SNPs was calculated using the PLINK clustering method, excluding SNPs with LD coefficient r^2 > 0.001 and within 10,000 kb to ensure SNP independence and reduce pleiotropic biases. 3. Statistical Strength Configuration: The robustness of instrumental variables was assessed using the F-statistic (F = β^2/SE^2), with variables having F < 10 deemed inadequate to mitigate confounding effects.

Leveraging GWAS data, SNPs associated with the instrumental variables were identified, and through the “harmonise_data” function within TwoSampleMR, we aligned allelic directions of exposure and outcome, excluding incompatible SNPs. The inverse variance-weighted (IVW) method served as the cornerstone for causal inference, employing the variance of instrumental variables as weights to determine causal dynamics, thereby advancing our understanding of the genetic architecture underlying disease states.

Active components-targets docking

ADCY4 and PNPT1 were docked to verify the accuracy of principal components and prediction targets. The protein configurations of the core targets were obtained from the Uniprot database by using the minimum resolution (Resolution) and the source (Method) as X-ray as the screening condition, and the crystal structure of these protein configurations were obtained from the RCSB PDB database). 2D structures of 6 active components of core targets were obtained from PubChen database, and these 2D structures were minimized by chem3d software. The binding strength and activity of active components and targets were evaluated by SYBYL2.0 software, and the active components of binding TotalScore greater than 3 were selected for sub-docking. Then imported the crystal into the Pymol 2.4 for dehydration, hydrogenation, and separation of ligands; it then imported AutoDockTools 1.5.6 to construct the docking grid box for each target. Docking was completed by Vina 1.1.2 software, and the molecules with the lowest binding energy in the docking conformation were selected to observe the binding effect by matching with the original ligands and intermolecular interactions (such as hydrophobicity, cation-π, anion-π, π-π stacking, hydrogen bonding, etc.). Finally, the Pymol2.4 software was utilized to visualize the molecular docking.

Identification of DEGs and principal component analysis

Among the 31 examined PyMGs, several exhibited significant differences in expression levels. Furthermore, gene clustering analysis revealed distinct clusters in the treatment and control groups. Notable PyMGs in the treatment group included DHODH, POLE, UCK2, ENTPD1, NT5E, UPB1, ENPP1, TXNRD1, while control group PyMGs comprised PNPT1, POLR3F, PRIM2, POLR2C, POLR2G, POLR1D, POLR2B (Fig.  2 a). Correlation analysis was conducted among these PyMGs, and a correlation matrix was generated for visualization (Fig.  2 b) (Table S2).

Principal Component Analysis. a Analysis of difference. b Analysis of correlation

Enrichment analysis of PyMGs

GO enrichment analysis identified 290 core target genes, encompassing BP, MF, and CC. The MF category primarily involved nucleoside binding (GO: 0001882), catalytic activity, acting on RNA (GO: 0140098), ribonucleoside binding (GO: 0032549). The CC category was mainly associated with transferase complex, transferring phosphorus-containing groups (GO: 0061695), nuclear chromosome (GO: 0000228), RNA polymerase complex (GO: 0030880). The BP category included RNA splicing (GO: 0008380), anatomical structure homeostasis (GO: 0060249), purine-containing compound metabolic process (GO: 0072521). KEGG enrichment analysis revealed that the upregulated genes were primarily involved in Pyrimidine metabolism (hsa00240), Huntington's disease (hsa05016), Purine metabolism (hsa00230) (Fig.  3 and Table S3a, b).

For PyMGs, GO, and KEGG analyses were performed. a The GO circle illustrates the scatter map of the selected gene’s logFC. b The KEGG barplot and bubble illustrates the scatter map of the logFC of the indicated gene

Model construction

In our study, we meticulously established a gene signature by employing LASSO and Cox regression analysis, judiciously selecting the optimal value, as depicted in Fig.  4 a, b. To validate the precision and reliability of our model, we constructed a machine learning model using SVM-RFE. This model demonstrated exceptional accuracy, achieving a score of 0.863, and maintained a minimal error rate of 0.137, as shown in Fig.  4 c, d. Some key genes were screened by random forest tree, including NME7, POLR3C, ENTPD4, ENPP1, UCKL1, etc. (Fig.  4 e, f). The intersection of the 11 PyMGs identified by LASSO, RF and SVM revealed strong concordance (Fig.  4 g). Upon evaluating the model in relation to the 11 hub genes, we observed notably high accuracy rates for each gene: DHODH (AUC = 0.680), UMPS (AUC = 0.823), NME7 (AUC = 0.776), NME1 (AUC = 0.767), POLR2B (AUC = 0.672), POLR3B (AUC = 0.775), POLR1C (AUC = 0.637), POLE (AUC = 0.699), ENPP3 (AUC = 0.679), RRM2B (AUC = 0.744), TK2 (AUC = 0.720) (Fig.  4 f). Remarkably, an AUC of 0.934 (95% CI 0.887−0.973) was achieved in dataset GSE76262, underscoring the high accuracy and robustness of our prediction model (Fig.  4 g) (Table  1 and S4). In evaluating the performance of our study, particularly with regard to the AUC, a detailed analysis of Fig.  4 demonstrates an impressive AUC value of 0.934, underscoring the high accuracy of our model. Addressing concerns about the lower AUC values observed for certain genes, it is essential to consider the influence of individual genetic variations on these outcomes. Despite these variations, it is important to note that the aggregated AUC values for these genes consistently approximate a significant benchmark of 0.7. This collective result substantiates the overall credibility, precision, and robustness of our predictive model, affirming its utility in both clinical and research contexts.

The development of the PyMGs signature. a Regression of the 11 Asthma-related genes using LASSO. b Cross-validation is used in the LASSO regression to fine-tune parameter selection. c , d Accuracy and error of this model. e , f : RF. g Venn. h AUC of 10 hub genes. i AUC of train group

Gene set enrichment analysis

In this study, the AUC of each gene in the test group, the Rank ranking of each gene, and the results of the test group validation were observed. We found that NME7 and POLR2B may be the most relevant genes. Through literature evaluation and analysis of hub gene sensitivity within the model, it was determined that NME7 and POLR2B may be the most relevant genes to Asthma. In terms of GO analysis, NME7 was found to be associated with CC ribosome, MF cytokine receptor activity, MF structural constituent of ribosome. On the other hand, POLR2B was primarily involved in the CC mitochondrial protein containing complex, CC organellar ribosome, CC ribosomal subunit (Fig.  5 a). In KEGG analysis, NME7 was mainly associated with cytokine cytokine receptor interaction, neuroactive ligand receptor interaction, oxidative phosphorylation, while POLR2B was involved in neuroactive ligand receptor interaction, oxidative phosphorylation, parkinsons disease (Fig.  5 b) (Table S5).

GSEA of Analysis in NME7 and POLR2B. a GO. b KEGG

Analysis of immune cells

In this investigation, we explore the nuanced role of the immune microenvironment in the onset and progression of asthma, a complex condition shaped by the dynamics of immune cell interactions. Our extensive analysis was designed to unravel the expression patterns and interrelations of these cells, utilizing violin plots to vividly delineate the differential expression profiles of immune cells in control versus asthma-impacted tissues. These graphical representations distinctly showcased an upregulation of activated mast cells, eosinophils, and both resting and activated dendritic cells in the control samples. Conversely, tissues afflicted by asthma exhibited heightened levels of CD8 T cells, follicular helper T cells, and both M0 and M2 macrophages, illuminating the altered or engaged immune response mechanisms in asthma. This endeavor aimed to elucidate the potential genetic interplays with, or influences by, the immune microenvironment in asthma, striving to enrich our comprehension of the disease's pathophysiological underpinnings. The results, showcased in Fig.  6 a, reveal a complex symbiosis between immune cells and genetic factors, broadening our understanding of the intricate immune-genetic interplay in asthma. In addition, we added NME7 and POLR2B to the immune infiltration analysis of their respective genes alone.

Expression of Immune cells. a Expression of immune cells in different clusters. b NME7. c POLR2B

In the GO analysis, NME7 was primarily associated with CC septin cytoskeleton, BP negative regulation of myoblast proliferation, BP axonemal central apparatus assembly, MF olfactory receptor binding, CC iga immunoglobulin complex. POLR2B was mainly involved in the MF udp xylosyltransferase activity, BP regulation of mirna catabolic process, BP positive regulation of mirna catabolic process, CC fancm mhf complex, MF glycine n acyltransferase activity (Fig.  7 a). In terms of KEGG analysis, NME7 was mainly associated with glycosaminoglycan degradation, taurine and hypotaurine metabolism, renin angiotensin system, glycosphingolipid biosynthesis lacto and neolacto series, asthma, sulfur metabolism. POLR2B was involved in glycosaminoglycan biosynthesis heparan sulfate, linoleic acid metabolism, arachidonic acid metabolism, taste transduction, retinol metabolism, nitrogen metabolism (Fig.  7 b).

GSVA of Analysis in NME7 and POLR2B. a GO. b KEGG

Drug-gene interactions

Some drugs were predicted to interact with the eleven hub genes, including leflunomide, teriflunomide, vidofludimus, chembl1164954, leucovorin (Table S6) (Fig.  8 ). The investigation unveiled eleven PyMGs—DHODH, UMPS, NME7, NME1, POLR2B, POLR3B, POLR1C, POLE, ENPP3, RRM2B, TK2—significantly associated with asthma. According to rank, NME7 and POLR2B were selected for molecular docking. To verify the credibility of our results. We performed molecular docking of NME7 and POLR2B with CHEMBL1164954, LEFLUNOMIDE, TERIFLUNOMIDE, ZALCITABINE (Table  2 and Fig.  9 ).

Drug-gene interactions. Red circles are up-regulated genes, green hexagons are down-regulated genes, and blue squares are associated drugs

Molecular docking results. a UMPS. b DHODH

Identification of common RNAs and construction of miRNA-lncRNA shared genes network

A total of 212 miRNAs and 241 lncRNAs associated with Asthma were identified from three databases (Table S7a, b). Table S7 shows the matching of these genes against the corresponding miRNA database. These databases include miRanda [ 17 ], miRDB [ 18 ], and TargetScan [ 19 ]. When the corresponding database matched the relevant miRNA, the score was marked as 1. It can be seen that when all three databases can be matched, it is 3 points. The miRNA was matched by spongeScan database [ 20 ] to obtain the corresponding lncRNA data. The miRNA-lncRNA-gene network was constructed by intersecting these non-coding RNAs with the shared genes obtained through Lasso regression and SVM-RFE. The network consisted of 190 lncRNAs, 182 miRNAs, and some common genes, including the 11 hub genes (NME7, TK2, UMPS, POLE, ENPP3, POLR1C, DHODH, RRM2B, POLR3B, NME1, POLR2B) (Fig.  10 ).

miRNAs-LncRNAs shared Genes Network. Red circles are mrnas, blue quadrangles are miRNAs, and green triangles are lncRNAs

Validation of hub genes

To enhance the confidence and prediction accuracy of the model, GSE147878 dataset was used for validation. The GSE147878 analysis further confirming their potential relevance to Asthma (Fig.  11 ).

eleven hub genes were validated

Model verification

The Boxplots depicted the residual expression patterns of these genes in Asthma (Fig.  12 a). There are some differences in the proportions of the four different modes (Fig.  12 b, c). The PyMGs' diagnostic capacity in distinguishing Asthma from control samples revealed a satisfactory diagnostic value, with an AUC of RF: 0.967; SVM: 0.919; XGB: 0.943; GLM: 0.933 (Fig.  12 c). An AUC of 1.000 (95% CI 1.000–1.000) in GSE147878 (Fig.  12 d).

Model verification. a Residual expression patterns. b , c Model expression patterns ( d ) AUC of model. e AUC of test group

In our exploration of the intrinsic connection between NME7 and POLR2B, and asthma forest plots were meticulously employed to visually articulate the associations. For NME7, the all SNPs (rs73078636, rs10178845, rs11071559, rs2460555, rs7734635, rs5743618, etc.) conspicuously positioned itself to the right of the confidence interval, indicating a positive association. (Fig.  13 a). In the case of POLR2B, all SNPs (rs10178845, rs11071559, rs2460555, rs7734635, rs5743618, rs61957178, rs4795399, etc.) were all situated to the right of the confidence interva, suggesting a similar trend of association with asthmal (Fig.  13 b). Further dissecting the heterogeneity inherent in our analysis, the funnel plot tailored to asthma revealed a deviation from the expected symmetrical distribution, albeit maintaining a general symmetry. This nuanced observation was further scrutinized through sensitivity analysis, employing a “leave-one-out” approach. Remarkably, the omission of any individual SNP from the analysis had a negligible effect on the results of the Inverse Variance Weighted (IVW) analysis, indicating that the remaining SNPs consistently mirrored the outcomes of the aggregate dataset. Substantiating the validity of our findings, the MR-Egger regression analysis was invoked, providing a solid foundation that bolsters both the robustness and authenticity of our results and the methodologies applied. This Mendelian randomization analysis unequivocally confirms the intimate association of NME7 and POLR2B with asthma. Hence, it delineates a potential pathway to modulate the incidence, evolution, and progression of asthma by intervening in the functions of NME7 and POLR2B, presenting a promising avenue for therapeutic intervention and a deeper understanding of the disease mechanism.

Mendelian Randomization Analysis. a NME7. b POLR2B

Discussions

Asthma, a chronic inflammatory disorder of the airways, presents a significant global health challenge, with the Global Asthma Network (GAN) study reporting prevalence rates of 10.5% in children and 4.4% in adults [ 21 ]. Characterized by airway inflammation, hyperresponsiveness, mucus hypersecretion, and remodeling, the pathophysiology of asthma is complex, resulting from a multifaceted interplay of genetic and environmental factors [ 22 ]. Despite the availability of treatments primarily aimed at symptomatic relief, a substantial proportion of patients remain inadequately managed, highlighting the urgent need for advanced therapeutic interventions [ 23 ]. In this context, the identification of asthma biomarkers through comprehensive bioinformatic analysis is a critical endeavor. This approach aims to unravel the complex mechanisms underlying asthma and uncover novel therapeutic targets, potentially shifting asthma management towards early detection and precise disease characterization [ 24 ]. PyM is essential for the synthesis, breakdown, and utilization of key pyrimidine nucleobases, such as cytosine and uracil, which are integral to nucleic acid structures and energy metabolism [ 8 ]. Dysregulation of PyM pathways is implicated in various inherited metabolic disorders, including autoimmune inflammatory diseases [ 9 ]. Recent studies have highlighted the role of microRNAs, such as miR-146a and miR-155, in modulating cell proliferation in asthma by targeting genes that inhibit cell growth, and the TSHR-mediated regulation of these microRNAs in asthma's fibroproliferative pathology [ 10 ]. Additionally, research has identified dysregulation in PPP2R2B (B55ß) through inflammation-driven hypermethylation, affecting apoptosis resistance, and the role of UBE2T in exacerbating hepatocellular carcinoma by influencing PyM [ 12 ]. This study focuses on PyMGs and their relevance in asthma immunotherapy, exploring new therapeutic avenues through the investigation of purinosome formation and the glutamine pyrimidine metabolism pathway [ 25 ]. Despite advancements, the impact of PyM on the immunogenic landscape and its role in modulating immunotherapy efficacy in asthma remains to be fully elucidated. Our research aims to conduct a thorough analysis of PyMGs and their interaction with immunotherapeutic strategies in asthma, paving the way for groundbreaking clinical progress.

In our comprehensive study, we identified a network of 31 DEGs intricately associated with PyMGs in asthma. Utilizing a rigorous analytical framework that combines DEG analysis, Lasso regression, and SVM-RFE, we identified eleven critical PyMGs: DHODH, UMPS, NME7, NME1, POLR2B, POLR3B, POLR1C, POLE, ENPP3, RRM2B, and TK2. These genes have demonstrated significant diagnostic relevance in asthma, a finding further validated by external datasets, underscoring their essential role in the disease's pathogenesis. However, our research also revealed a significant gap in understanding the interaction between these genes and specific transcription factors, especially within the context of purine metabolism. Notably, NME7 and POLR2B emerged as key mediators in the link between asthma and PyMGs. Further investigation into their biological functions indicated their involvement in various immune-related processes, including RNA splicing, anatomical structure homeostasis, and the metabolic processing of purine-containing compounds. This finding suggests that PyMGs may regulate a broad spectrum of biological pathways, particularly those related to immune responses, thereby potentially influencing the pathophysiological progression of asthma. Our results propose that these genes are crucial in understanding asthma’s progression and could unveil new avenues for therapeutic targeting, presenting promising opportunities for future research and the development of treatment strategies. This underscores the paramount importance of PyMGs within the molecular landscape of asthma, indicating a novel direction in the quest to understand and mitigate this complex disease.

The investigation into PyM, a cornerstone of cellular energy balance and proliferation, has revealed its extensive implications across various diseases and metabolic disorders. In the intricate landscape of asthma pathogenesis, recent research has highlighted the critical roles of NME7 and POLR2B in shaping the molecular framework of this disease. Asthma, characterized by chronic airway inflammation, hyperresponsiveness, and reversible airflow obstruction, arises from a complex interplay of genetic, environmental, and immunological factors [ 26 ]. Identifying NME7 and POLR2B as key players in this intricate narrative adds a new dimension to our understanding of asthma's origins and potential therapeutic avenues. NME7, associated with intracellular signaling and cellular differentiation pathways, has been significantly linked to asthma [ 27 ]. Its role in modulating signal transduction pathways underscores its impact on the inflammatory cascade and airway smooth muscle cell dynamics, which are integral to asthma's pathophysiology [ 28 ]. However, the precise mechanisms by which NME7 influences asthma require further elucidation. The gene's association with asthma suggests that any deviation in NME7's expression or functionality could exacerbate the inflammatory environment, leading to increased asthma symptoms and airway structural changes [ 29 ]. Similarly, POLR2B, a vital component of the RNA polymerase II complex essential for mRNA synthesis, has been identified as a gene of interest in asthma research. Its fundamental role in gene expression regulation positions POLR2B as a key mediator in asthma by controlling genes involved in immune responses and airway inflammation [ 30 ]. Changes in POLR2B expression or function could alter the transcriptional profile of asthma-related genes, influencing disease severity and the effectiveness of therapeutic interventions. Furthermore, analyses of the GSE147878 dataset have highlighted PyM-related markers as emerging prognostic indicators in asthma, representing a dynamic frontier in genomic exploration. These insights pave the way for innovative therapeutic strategies in asthma management, heralding the advent of personalized medicine in contemporary healthcare. This body of research not only deepens our understanding of asthma's molecular etiology but also underscores the potential of targeted genetic and molecular interventions in revolutionizing asthma treatment paradigms.

Asthma, a chronic disorder, is characterized by persistent airway inflammation and increased reactivity, resulting from a complex interplay between host immune mechanisms and environmental factors within the pulmonary environment. The pathogenesis of asthma is marked by an imbalance between the innate and adaptive immune systems in the airways [ 31 ]. Environmental triggers—such as allergens, pollutants, and respiratory pathogens—induce airway epithelial cells to initiate an immune response, characterized by the release of pro-inflammatory cytokines and chemokines. This response recruits various innate immune cells, including neutrophils, macrophages, dendritic cells, and innate lymphoid cells, leading to acute inflammation [ 32 ]. Simultaneously, dysregulation of adaptive immune responses, particularly within T-helper (Th) cell subsets, plays a crucial role in sustaining chronic inflammation and structural changes characteristic of asthma [ 33 ]. A shift towards Th2-dominated responses, marked by the secretion of interleukins (IL)-4, IL-5, and IL-13, promotes eosinophilic inflammation, airway hyperresponsiveness, and excessive mucus production [ 34 ]. Additionally, recent studies have highlighted the significant roles of aberrant Th17 and regulatory T cell (Treg) functions in modulating airway inflammation and remodeling, adding complexity to our understanding of asthma’s immunology. Our analysis, utilizing violin plot visualizations, has identified distinct immune cell expression profiles. The control group exhibited higher levels of activated mast cells, eosinophils, and both resting and activated dendritic cells. In contrast, the treatment group showed increased levels of CD8 T cells, follicular helper T cells, and both M0 and M2 macrophages. These findings provide deeper insights into the immune landscape of asthma. These observations underscore the importance of elucidating immune pathways to advance innovative therapeutic strategies. Immunomodulatory interventions, aimed at reducing inflammation and correcting immune dysregulation, present a promising avenue for novel asthma treatments. This research heralds a new era in targeted therapeutic interventions, poised to reshape the future of asthma therapy by emphasizing the critical role of immune pathways in understanding and managing the disease.

The merging of asthma research with metabolic studies marks a groundbreaking phase in medical science, energized by the adoption of advanced bioinformatics techniques. This shift has significantly broadened our understanding of the molecular complexity and diverse pathological expressions of asthma [ 35 , 36 , 37 ]. The scientific community's collaborative efforts have been crucial in deciphering the molecular foundations and clinical spectrum of this disease. Our research represents a pivotal advancement in this burgeoning field, highlighting the critical role of PyMGs within the asthma paradigm. Utilizing extensive datasets from the GEO, specifically GSE76262 and GSE147878, we have applied a comprehensive suite of analytical tools, including GO, KEGG, and GSEA. These tools have enabled the development of a sophisticated predictive model that illuminates the intricate role of PyMGs in asthma's etiology. Our work establishes a foundational theoretical framework while also opening new pathways for investigating the metabolic imbalances at the heart of asthma and developing targeted therapeutic approaches. However, the necessity for further empirical research to confirm the mechanisms proposed in our findings is paramount. Such validation, achievable through rigorous in vivo and in vitro testing, is essential to deepen our understanding of asthma. These exacting scientific endeavors are vital for progressing towards effective treatment solutions, shaping the future of asthma research and therapeutic development.

Within the complex landscape of asthma, PyMGs play a central role, orchestrating a broad array of biological interactions, pathways, signaling cascades, and regulatory mechanisms. At the core of asthma's molecular framework, PyMGs underlie the synthesis of key biomolecules such as DHODH, UMPS, NME7, NME1, POLR2B, POLR3B, POLR1C, POLE, ENPP3, RRM2B, and TK2, which are crucial in essential physiological processes and metabolic regulation related to asthma. Notably, NME7 and POLR2B are distinguished by their significant regulatory effects on metabolic pathways, profoundly influencing asthma's pathophysiological terrain. Our investigations into PyMGs highlight their vital role in the metabolic imbalances characteristic of asthma, proposing the targeting of these pathways as a viable therapeutic strategy.

Availability of data and materials

The datasets generated and/or analysed during the current study are available in the [GEO] repository. https://www.ncbi.nlm.nih.gov/geo/ .

Abbreviations

Gene ontology

Traditional Chinese medicine

Molecular functions

Kyoto encyclopedia of genes and genomes

Gene expression omnibus

Pyrimidine metabolism genes

Biological processes

Cellular components

Differentially expressed genes

Gomez JL. Epigenetics in asthma. Curr Allergy Asthma Rep. 2019;19(12):56.

Article   PubMed   PubMed Central   Google Scholar  

Lauzon-Joset JF, Marsolais D, Tardif-Pellerin E, Patoine D, Bissonnette EY. CD200 in asthma. Int J Biochem Cell Biol. 2019;112:141–4.

Article   PubMed   CAS   Google Scholar  

Cormier M, Lemiere C. Occupational asthma. Int J Tuberc Lung Dis. 2020;24(1):8–21.

Pinyochotiwong C, Chirakalwasan N, Collop N. Nocturnal asthma. Asian Pac J Allergy Immunol. 2021;39(2):78–88.

PubMed   CAS   Google Scholar  

Khan DA, Oppenheimer JJ, Lee GB, Fineman SM. Asthma. Ann Allergy Asthma Immunol. 2019;123(4):416–7.

Article   PubMed   Google Scholar  

Katwa U, Kabra SK. Advances in asthma. Indian J Pediatr. 2018;85(8):641–2.

Garavito MF, Narvaez-Ortiz HY, Zimmermann BH. Pyrimidine metabolism: dynamic and versatile pathways in pathogens and cellular development. J Genet Genomics. 2015;42(5):195–205.

El KM. Pyrimidine metabolism in schistosomes: a comparison with other parasites and the search for potential chemotherapeutic targets. Comp Biochem Physiol B Biochem Mol Biol. 2017;213:55–80.

Article   Google Scholar  

Pfenninger KH. Plasma membrane expansion: a neuron’s Herculean task. Nat Rev Neurosci. 2009;10(4):251–61.

Woeller CF, Roztocil E, Hammond C, Feldon SE. TSHR signaling stimulates proliferation through PI3K/Akt and induction of miR-146a and miR-155 in thyroid eye disease orbital fibroblasts. Invest Ophthalmol Vis Sci. 2019;60(13):4336–45.

Article   PubMed   PubMed Central   CAS   Google Scholar  

Madera-Salcedo IK, Sanchez-Hernandez BE, Svyryd Y, Esquivel-Velazquez M, Rodriguez-Rodriguez N, Trejo-Zambrano MI, Garcia-Gonzalez HB, Hernandez-Molina G, Mutchinick OM, Alcocer-Varela J, et al. PPP2R2B hypermethylation causes acquired apoptosis deficiency in systemic autoimmune diseases. JCI Insight. 2019. https://doi.org/10.1172/jci.insight.126457 .

Zhu Z, Cao C, Zhang D, Zhang Z, Liu L, Wu D, Sun J. UBE2T-mediated Akt ubiquitination and Akt/beta-catenin activation promotes hepatocellular carcinoma development by increasing pyrimidine metabolism. Cell Death Dis. 2022;13(2):154.

Yuan Y, Li N, Fu M, Ye M. Identification of critical modules and biomarkers of ulcerative colitis by using WGCNA. J Inflamm Res. 2023;16:1611–28.

Xu M, Kong Y, Chen N, Peng W, Zi R, Jiang M, Zhu J, Wang Y, Yue J, Lv J, et al. Identification of immune-related gene signature and prediction of CeRNA network in active ulcerative colitis. FRONT IMMUNOL. 2022;13:855645.

Wu Y, Liu X, Li G. Integrated bioinformatics and network pharmacology to identify the therapeutic target and molecular mechanisms of Huangqin decoction on ulcerative Colitis. Sci Rep. 2022;12(1):159.

Wu Z, Liu P, Huang B, Deng S, Song Z, Huang X, Yang J, Cheng S. A novel Alzheimer’s disease prognostic signature: identification and analysis of glutamine metabolism genes in immunogenicity and immunotherapy efficacy. Sci Rep. 2023;13(1):6895.

De Carvalho TR, Giaretta AA, Teixeira BF, Martins LB. New bioacoustic and distributional data on Bokermannohyla sapiranga Brandao et al., 2012 (Anura: Hylidae): revisiting its diagnosis in comparison with B. pseudopseudis (Miranda-Ribeiro, 1937). Zootaxa. 2013;3746:383–92.

Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2020;48(D1):D127–31.

Mon-Lopez D, Tejero-Gonzalez CM. Validity and reliability of the TargetScan ISSF Pistol & Rifle application for measuring shooting performance. Scand J Med Sci Sports. 2019;29(11):1707–12.

Furio-Tari P, Tarazona S, Gabaldon T, Enright AJ, Conesa A. spongeScan: a web for detecting microRNA binding elements in lncRNA sequences. Nucleic Acids Res. 2016;44(W1):W176–80.

Williams EJ, Berthon BS, Stoodley I, Williams LM, Wood LG. Nutrition in asthma. Semin Respir Crit Care Med. 2022;43(5):646–61.

Guerau-de-Arellano M, Britt RJ. Sterols in asthma. Trends Immunol. 2022;43(10):792–9.

Quirt J, Hildebrand KJ, Mazza J, Noya F, Kim H. Asthma. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):50.

King-Biggs MB. Asthma. Ann Intern Med. 2019;171(7):C49–64.

Liu C, Gu C, Huang W, Sheng X, Du J, Li Y. Targeted UPLC-MS/MS high-throughput metabolomics approach to assess the purine and pyrimidine metabolism. J Chromatogr B Analyt Technol Biomed Life Sci. 2019;1113:98–106.

Sedova L, Bukova I, Bazantova P, Petrezselyova S, Prochazka J, Skolnikova E, Zudova D, Vcelak J, Makovicky P, Bendlova B, et al. Semi-lethal primary ciliary dyskinesia in rats lacking the Nme7 gene. Int J Mol Sci. 2021. https://doi.org/10.3390/ijms22083810 .

Sedova L, Prochazka J, Zudova D, Bendlova B, Vcelak J, Sedlacek R, Seda O. Heterozygous Nme7 mutation affects glucose tolerance in male rats. Genes. 2021. https://doi.org/10.3390/genes12071087 .

Ren X, Rong Z, Liu X, Gao J, Xu X, Zi Y, Mu Y, Guan Y, Cao Z, Zhang Y, et al. The protein kinase activity of NME7 activates Wnt/beta-catenin signaling to promote one-carbon metabolism in hepatocellular carcinoma. Cancer Res. 2022;82(1):60–74.

Sun Y, Li S, Li H, Yang F, Bai Y, Zhao M, Guo J, Zhao M, Zhou P, Khor CC, et al. TNFRSF10A-LOC389641 rs13278062 but not REST-C4orf14-POLR2B-IGFBP7 rs1713985 was found associated with age-related macular degeneration in a Chinese population. Invest Ophthalmol Vis Sci. 2013;54(13):8199–203.

Li XL, Xie Y, Chen YL, Zhang ZM, Tao YF, Li G, Wu D, Wang HR, Zhuo R, Pan JJ, et al. The RNA polymerase II subunit B (RPB2) functions as a growth regulator in human glioblastoma. Biochem Biophys Res Commun. 2023;674:170–82.

Wang H, Jia Y, Gu J, Chen O, Yue S. Ferroptosis-related genes are involved in asthma and regulate the immune microenvironment. Front Pharmacol. 2023;14:1087557.

Yip W, Hughes MR, Li Y, Cait A, Hirst M, Mohn WW, McNagny KM. Butyrate shapes immune cell fate and function in allergic asthma. Front Immunol. 2021;12:628453.

Shamji MH, Sharif H, Layhadi JA, Zhu R, Kishore U, Renz H. Diverse immune mechanisms of allergen immunotherapy for allergic rhinitis with and without asthma. J Allergy Clin Immunol. 2022;149(3):791–801.

Strzelak A, Ratajczak A, Adamiec A, Feleszko W. Tobacco smoke induces and alters immune responses in the lung triggering inflammation, allergy, asthma and other lung diseases: a mechanistic review. Int J Environ Res Public Health. 2018. https://doi.org/10.3390/ijerph15051033 .

Huang F, Yu J, Lai T, Luo L, Zhang W. The combination of bioinformatics analysis and untargeted metabolomics reveals potential biomarkers and key metabolic pathways in asthma. Metabolites. 2022. https://doi.org/10.3390/metabo13010025 .

Chen ST, Yang N. Constructing ferroptosis-related competing endogenous RNA networks and exploring potential biomarkers correlated with immune infiltration cells in asthma using combinative bioinformatics strategy. BMC Genomics. 2023;24(1):294.

Wu Z, Cai Z, Shi H, Huang X, Cai M, Yuan K, Huang P, Shi G, Yan T, Li Z. Effective biomarkers and therapeutic targets of nerve-immunity interaction in the treatment of depression: an integrated investigation of the miRNA-mRNA regulatory networks. Aging. 2022;14(8):3569–96.

Download references

The Second “Xinglin Scholars-Nursing Youth” Program of Shanghai University of Traditional Chinese Medicine (2023HLXL09); Science and Technology Development Project (Nursing Special Project), Shanghai University of Traditional Chinese Medicine 23HLZX06.

Author information

Dihui Zhang and Xiaowei Pu contributed equally to this article as the first author.

Authors and Affiliations

Orthopedics department The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, 510000, China

Dihui Zhang

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China

Xiaowei Pu & Jia Chen

Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, 257091, Shandong, People’s Republic of China

Man Zheng & Guanghui Li

You can also search for this author in PubMed   Google Scholar

Contributions

Dihui Zhang and Xiaowei Pu drafted and revised the manuscript. Dihui Zhang and Man Zheng were in charge of data collection. Dihui Zhang and Xiaowei Pu were in charge of design of frame. Jia Chen and Guanghui Li conceived and designed this article, in charge of syntax modification and revised of the manuscript. All the authors have read and agreed to the final version manuscript.

Corresponding authors

Correspondence to Guanghui Li or Jia Chen .

Ethics declarations

Ethics approval and consent to participate.

Not applicable.

Consent for publication

Competing interests.

The authors declare no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1, rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ .

Reprints and permissions

About this article

Cite this article.

Zhang, D., Pu, X., Zheng, M. et al. Employing a synergistic bioinformatics and machine learning framework to elucidate biomarkers associating asthma with pyrimidine metabolism genes. Respir Res 25 , 327 (2024). https://doi.org/10.1186/s12931-024-02954-4

Download citation

Received : 29 March 2024

Accepted : 17 August 2024

Published : 31 August 2024

DOI : https://doi.org/10.1186/s12931-024-02954-4

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Pyrimidine metabolism-related genes (PyMGs)
• Lasso regression
• Bioinformatics

Respiratory Research

ISSN: 1465-993X

• General enquiries: [email protected]

beta This is a new service – your feedback will help us to improve it.

• Search agreements
• Professional Services

Search agreements in Professional Services category

Apply filters, filter by agreement status, upcoming agreements.

View our upcoming agreement page for agreements that are being developed and are not yet live.

Browse by category

• Financial Services
• HR and Workforce Services
• Outsourced Services
• Travel, Accommodation and Venues
• Construction
• Estates Support Services
• Facilities Management
• Cloud and Hosting
• Digital Capability and Delivery
• Network Services
• Software and Hardware
• Technology Services

14 agreements found

Audit & assurance services (a&as).

• Agreement ID: RM6188
• Start Date: 11/08/2021
• End Date: 10/08/2025

Access audit and assurance services including internal and external audit, counter fraud and investigation.

Campaign Solutions 2

• Agreement ID: RM6125
• Start Date: 07/09/2021
• End Date: 06/09/2025

UK government and public sector bodies can access the services they need for end to end campaign solutions to support the running of their public service campaigns.

Communications Marketplace

• Agreement ID: RM6124
• Start Date: 06/09/2021
• End Date: 04/09/2027

A Marketplace for marketing and communications services to help UK government and public sector bodies run public service campaigns.

Costs Lawyer Services 2

• Agreement ID: RM6284
• Start Date: 25/07/2023
• End Date: 24/07/2026

All public sector organisations can access costs law services including law advice and consultancy and negotiation.

Language Services

• Agreement ID: RM6141
• Start Date: 10/05/2021
• End Date: 09/05/2025

Language Services including translation, transcription, interpreting and a quality assurance service. Available to the whole of the public and third sector.

Legal Services Panel

• Agreement ID: RM6179
• Start Date: 01/12/2021
• End Date: 30/11/2025

General legal advice and services for central government, including finance and complex legal services. Provides for a wide range of commonly needed areas of law, including contracts, dispute resolution and litigation, real estate and corporate finance.

Management Consultancy Framework Three (MCF3)

• Agreement ID: RM6187
• Start Date: 24/08/2021
• End Date: 23/08/2025

Access to consultancy including business, strategy and policy, finance, HR, procurement, health/social care and community, infrastructure and environment.

Media Services

• Agreement ID: RM6123
• Start Date: 14/12/2021
• End Date: 13/12/2025

Central government and the wider public sector (WPS) can buy a world class communication service through the buying of advertising space, partnerships and out of home advertising (OOH), as well as services to audit the performance of their agencies and the opportunity to monetise their own advertising estate.

Public Sector Legal Services

• Agreement ID: RM6240
• Start Date: 06/09/2022
• End Date: 05/09/2026

This framework has been established to provide a simple and compliant route to market for a range of legal services requirements primarily to the wider public sector. It covers a wide range of commonly needed areas of law, including contracts, dispute resolution and litigation, contracts and corporate law. Comprising 3 lots the framework offers both general and more specific legal services.

Rail Legal Services

• Agreement ID: RM6204
• Start Date: 22/02/2022
• End Date: 21/02/2026

The Department for Transport (DfT) and related organisations can use this agreement to access legal advice and support specific to rail services.  The wider public sector can not use this agreement.

Research & Insights

• Agreement ID: RM6126
• Start Date: 03/12/2021
• End Date: 02/12/2027

All public sector organisations can access social, economic and market research and behavioural insights services for projects of all sizes and values.

Restructuring & Insolvency Services

• Agreement ID: RM6269
• Start Date: 08/02/2022
• End Date: 07/02/2026

UK government and public sector bodies can access specialist restructuring and insolvency services from a range of suppliers in a cost effective way.

Trade Law Panel

• Agreement ID: RM6183
• Start Date: 01/02/2021
• End Date: 30/01/2025

Specialist legal advice and support for international trade law, disputes, and negotiations. Available to central government departments and devolved administrations.

eDisclosure and Review Services 2

• Agreement ID: RM6336
• Start Date: 07/03/2023
• End Date: 06/03/2027

Central government and the wider public sector can access disclosure services for a complete service following the Electronic Discovery Reference Model or by using select elements of this.