Use Case
Drug Discovery

Cell Atlases: An Engine For Drug Discovery

Cell atlases speed up drug discovery by revealing cell diversity and function, accelerating target validation, improving trials, and inspiring new therapies.

What Are Cell Atlases?

Cell atlases are comprehensive reference maps that detail the types, properties, and functions of cells within an organism, tissue, or organ. By cataloging cells at a granular level, these atlases provide insights into cellular diversity, organization, and interactions. They are constructed using advanced technologies like single-cell RNA sequencing (scRNA-seq), single-cell chromatin assays, and spatial transcriptomics, which allow scientists to capture molecular characteristics at the single-cell level.

One prominent example is the Human Cell Atlas (HCA) initiative, a global effort to map all human cells to understand health and diseases better. By creating detailed profiles of every cell type, researchers aim to uncover how different cells contribute to the functioning of organs and how alterations in cells can lead to diseases.

Cell atlases provide detailed insights into cellular diversity and function, accelerating drug discovery and development. They enable faster target validation, enhance clinical trial design, and unlock novel therapeutic strategies. This leads to more efficient drug discovery processes, potentially reducing time-to-market and increasing success rates. Investing in cell atlas technology gives pharmaceutical companies a competitive edge in developing next-generation treatments and personalized medicine approaches.

Evolution of Cell Atlases
From Static to Dynamic to Granular

2000: Completion of sequencing the entire human genome - Human Genome Project
‍2003: Launch of the Encyclopedia of DNA Elements (ENCODE) project
2010: Initiation of the Genotype-Tissue Expression (GTEx) project
2016:  Mapping All Human Cells - Human Cell Atlas Initiative (HCA)
2022: Public release of large-scale data from the HCA project.

How Pharma Companies Are Winning

Integrating Cell Atlases for Better Discovery

Cell Atlases can be leveraged to enhance drug discovery and development in several ways
1. Early-stage drug discovery
Disease Mechanisms: By mapping the cellular composition of diseased tissues, we can identify which cell types and states contribute to disease progression.

Target Identification: Understanding the specific genes and their activity in a disease can reveal new, more precise, and potentially more effective drug targets.
2. Personalized Medicine
Biomarker Discovery: Cell atlases can help identify biomarkers that predict how patients will respond to therapies.

Patient Stratification: Detailed cellular information allows for the classification of patients based on cellular profiles, leading to more tailored treatments.
3. Drug Efficacy and Safety
Off-target Effects: By knowing where potential drug targets are expressed across different cell types, companies can predict and minimize side effects.

Toxicology Studies: Cell atlases can identify vulnerable cell populations that might be adversely affected by a drug.

How Can Pharma Build Cell Atlases?

Step 01: Survey the Existing Data Landscape

Understanding Available Resources

Begin by exploring what single-cell data is already available in your therapeutic area. Some fields, like immuno-oncology, have abundant public datasets rich with relevant metadata, while others, such as metabolic diseases, may have limited data availability.

This step saves time and resources by leveraging publicly available information and helps you pinpoint specific areas where additional data is needed.

Step 02: Fill Data Gaps with Proprietary Data

Investing in Single-Cell Technologies

After identifying gaps in the existing data landscape, the next step is to generate proprietary single-cell data tailored to your specific needs. This creates a unique data asset within your organization, enhancing your competitive edge in drug discovery.

  • Choosing the Right Technology

Selecting the appropriate single-cell sequencing technology is crucial. Consider factors such as throughput, cost, sensitivity, and compatibility with your sample types. Options to consider include 10x Genomics, offers high-throughput single-cell sequencing solutions suitable for large-scale projects. Parse Biosciences - provides scalable and flexible single-cell sequencing kits ideal for various sample types, and Fluidigm C1 System - enables precise single-cell capture and preparation, beneficial for specific applications. Research each platform to determine which aligns best with your project's requirements. Consult with technology providers and consider conducting pilot studies to assess performance.

  • Operational Considerations

Generating and analyzing single-cell data can be challenging due to costs and technical requirements.

  • In-House vs. Outsourcing: Decide whether to build in-house capabilities or outsource data generation and analysis.
    • In-House Analysis: Requires investment in equipment and recruitment of skilled bioinformaticians.
    • Outsourcing: Collaborate with external facilities or partners to reduce overhead costs and access specialized expertise.

Academic sequencing facilities can provide could provide the initial outsourced support without significant overheads. Consider partnering with organizations that offer support in data generation and analysis. Nygen would be happy to assist you with our partner facilities across Europe, which can streamline the process and help overcome resource limitations.

Step 03: Leverage Your Cell Atlas for Discovery

Advanced Data Analysis and Interpretation

With your cell atlas in place, focus on extracting actionable insights to drive drug discovery. Utilize machine learning (ML) and deep learning (DL) models to analyze complex datasets and uncover patterns.

Querying the Atlas

Develop methods to effectively query your cell atlas:

  • Target Identification: Analyze gene expression profiles to identify potential drug targets based on gene durability and relevance to disease pathways.
  • Safety Assessment: Predict potential toxicity and cross-tissue effects to prioritize targets with minimal adverse effects.

Leveraging Analytics Platforms

Advanced analytics platforms can facilitate this process by providing tools for data analysis, visualization, and predictive modeling without the need for extensive in-house bioinformatics expertise. Platforms like Nygen Insights offer capabilities to query and analyze your cell atlas, supporting target identification and validation through advanced computational methods.

Regulatory Compliance and Ethical Considerations

  • It's important to ensure that public data being consumed has complete freedom to operate. Polluting intellectual property should be avoided. Nygen performs thorough due diligence on data provenance.
  • It's also important to make sure that the data has been processed and integrated with tools that give full freedom to operate. Nygen uses permissive Free and Open Source Software (FOSS) tools in data processing.
  • The data gathered needs ethical compliance and permissions from human subjects.

Are you unsure how to leverage your cell atlases effectively? Need support? Reach out to us to learn how we can assist with projects involving cell atlases. We can help accelerate target validation, refine inclusion criteria and endpoints, and explore novel therapeutic strategies.

Successes in Drug Discovery

1. AstraZeneca's Lung Cell Atlas for Respiratory Diseases

Overview:

AstraZeneca collaborated with academic institutions and research organizations to develop a comprehensive cell atlas of the human lung. This initiative aimed to map the diverse cell types and states within healthy and diseased lung tissue, providing valuable insights into respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD).

Application in Drug Discovery:

  • Target Identification:
    • By analyzing single-cell RNA sequencing data from lung tissues, researchers identified key cells and pathways involved in the inflammatory processes of asthma and COPD.
    • Thymic stromal lymphopoietin (TSLP), a cytokine produced by airway epithelial cells, was identified as a crucial mediator in initiating allergic inflammation.
  • Drug Development:
    • AstraZeneca, in partnership with Amgen, developed Tezepelumab, a monoclonal antibody that inhibits TSLP.
    • Clinical trials demonstrated that Tezepelumab significantly reduced asthma exacerbations in patients with severe, uncontrolled asthma.
  • Personalized Medicine:
    • The lung cell atlas enabled the identification of biomarkers for patient stratification, allowing for more targeted and effective therapeutic interventions.
Impact

Regulatory Milestones

Tezepelumab received Breakthrough Therapy Designation from the FDA and was approved for use in patients with severe asthma.

Advancement in Understanding

The cell atlas provided deeper insights into lung biology and disease mechanisms, facilitating the discovery of additional therapeutic targets.

2. Kidney Precision Medicine Project (KPMP) for Renal Diseases

Overview:

The Kidney Precision Medicine Project (KPMP) is an initiative funded by the National Institutes of Health (NIH) that aims to create a detailed cellular atlas of the human kidney. The project focuses on understanding the cellular and molecular alterations in acute kidney injury (AKI) and chronic kidney disease (CKD).

Application in Drug Discovery:

  • Pathophysiological Insights:
    • Cellular Mapping:
    • Pathway Identification:
      • The atlas uncovers dysregulated pathways and novel cellular interactions contributing to disease progression.
  • Target and Biomarker Discovery:
    • Therapeutic Targets:
      • Identification of novel targets allows for the development of drugs aimed at specific cell types or pathways.
    • Biomarkers:
      • Early detection biomarkers facilitate timely intervention and improve patient outcomes.
Impact

Enhanced Drug Development

Pharmaceutical companies can utilize the kidney cell atlas to develop targeted therapies that may halt or reverse kidney damage.

Clinical Applications

Personalized treatment strategies can be devised based on a patient's unique cellular profile.

Boosting R&D Return on Investment (ROI)
The Strategic Impact of Cell Atlas Integration - A Summary

Key HighlightsAdvantages for Pharmaceutical Companies
Maximizing Efficiency
Rapid Target Identification: Cell atlases provide comprehensive maps of cell types and their gene expression profiles, enabling quicker identification of novel drug targets.

Example: AstraZeneca used a lung cell atlas to identify thymic stromal lymphopoietin (TSLP) as a key target in asthma, expediting the development of Tezepelumab.

Streamlined Research: Access to detailed cellular data reduces the need for time-consuming exploratory experiments.
Reduced Time to Market: Accelerates early-stage research, shortening drug development timelines.

Cost Savings: Decreases R&D expenses by minimizing redundant experiments.

Competitive Edge: Being first to market can capture greater market share and revenue.
Reducing Risk and Costs
Predicting Off-Target Effects: Understanding where potential drug targets are expressed helps in anticipating side effects.

Example: The Kidney Precision Medicine Project (KPMP) cell atlas identifies cell types susceptible to nephrotoxicity, aiding in safer drug design.

Early Risk Mitigation: Identifying unsuitable candidates early prevents costly late-stage failures.
Cost Efficiency: Saves millions by reducing the likelihood of expensive phase III trial failures.

Enhanced Safety Profiles: Improves drug safety, increasing approval chances.

Resource Allocation: Allows for better investment in promising candidates.
Higher Clinical Success Rates
Improved Patient Stratification: Cell atlases help identify biomarkers for selecting patients most likely to respond to a therapy.

Example: Single-cell tumor atlases reveal expression of PD-1 on exhausted T cells, guiding the use of pembrolizumab in suitable patients.

Higher Efficacy: Tailoring treatments based on cellular profiles increases clinical trial success rates.
Increased Approval Rates: Higher probability of successful trials leads to more drug approvals.

Optimized Trial Design: Efficient trials save time and resources.

Market Access: Effective treatments reach patients sooner, generating revenue faster.
Strategic Advantages
Leadership in Innovation: Utilizing cell atlases positions companies at the forefront of cutting-edge research.

Personalized Medicine: Enables development of therapies tailored to individual cellular profiles.

Example: Companies leveraging single-cell genomics can enter emerging therapeutic areas ahead of competitors.
Market Differentiation: Offers unique products that stand out in the marketplace.

New Revenue Streams: Access to novel therapeutic areas can open up additional markets.

Attractive Partnerships: Innovation attracts collaborations and investment opportunities.
Long-Term Value Creation
Data Reusability: Cell atlas data can be applied across multiple projects and disease areas.

Knowledge Base Expansion: Builds a repository of cellular information enhancing future research.

Example: The Tabula Muris mouse cell atlas informs studies in immunology, oncology, and neuroscience, supporting various preclinical models.
Maximized Investment: Initial data generation continues to provide value over time.

Cross-Project Efficiency: Reduces need for duplicate data collection in future projects.

Innovation Platform: Facilitates discovery of new targets and pathways.
Streamlining Regulatory Approval Processes
Robust Mechanistic Data: Detailed cellular insights provide strong evidence of a drug's mechanism of action.

Facilitated Reviews: Comprehensive data packages can streamline the regulatory review process.

Example: Therapies with clear cellular targets and effects, supported by cell atlas data, may receive expedited approval pathways.
Faster Market Entry: Accelerated approvals allow earlier access to revenue streams.

Extended Market Exclusivity: More time on the market before patent expiration enhances profitability.

Regulatory Confidence: Strong scientific backing improves relationships with regulatory agencies.

The transformative power of cell atlases in drug discovery is clear. Now is the time to leverage this game-changing technology to revolutionize your R&D efforts. Nygen specializes in creating and integrating custom cell atlases that can propel your research to new heights.

Ready to accelerate your drug discovery pipeline?

Don't miss this opportunity to stay ahead in the competitive pharmaceutical landscape. Our expert team at Nygen is ready to guide you through the process of building and implementing cell atlases tailored to your specific needs.

Book a demo with Nygen today and discover how cell atlases transform your research, reduce costs and fast-track your path to breakthrough discoveries.