MetaBase and Genestack

A partnership to drive innovation.

Fast decisions, but also the right decisions

Biopharma companies have come to know that a deeper understanding of basic target and disease biology has a significant positive impact on clinical success. In a recent published study, for example, AstraZeneca found that 40% of its clinical failures due to efficacy had no target disease linkage established, while 82% of projects with efficacy biomarkers succeeded. (1)

The big pharma’s in-depth analysis of its pipeline successes and failures showed a clear correlation between an understanding of basic target and disease biology and project success.

“Projects that showed greater confidence in target validation, genetic target linkage to disease, or a stronger understanding of the role of the target in the disease etiology were less likely to fail owing to lack of efficacy,” company researchers wrote.

Pharma companies, developers of consumer products and other organizations that depend on scientific research to move their enterprises forward also understand that breakthrough innovations require an approach to discovery that brings together the best thinking and ideas wherever they may be found. In an increasingly competitive environment, innovative organizations know also that strategic decisions regarding the direction of their research must be made quickly. But making fast decisions is never enough – they also have to be the right decisions.

MetaBase, from Clarivate Analytics, arguably the most comprehensive manually curated database of mammalian biology data available today in both industry and academia, is one of the fundamental R&D resources that innovators turn to. MetaBase’s curation, by experts at the PhD level only, provides assurance to its users that they are tapping into the best quality information available.

For drugmakers, MetaBase can be used for biomarker discovery, target identification, drug resistance and sensitivity analysis, drug repositioning, drug combination discovery, pharmacology and toxicity assessment, disease/treatment mechanism reconstruction, patient stratification and more.

A single-point-of-truth

Integrating Metabase into the Genestack platform enables the powerful combination of public and private systems biology resources to be harnessed to its full potential.

Genestack is the trusted Life Science Data management platform that provides a single-point-of truth for biologists and bioinformaticians. The platform’s modular, extensible and collaborative environment enables users to organize a diverse multitude of data types for analysis, which can evolve as their needs change.

Genestack addresses common challenges encountered by many pharmaceutical organizations, where datasets from different studies and experiments are often in silos across many locations, making it difficult to find and access. Genestack makes all this data readily accessible for any of the standardized and customized pipeline analysis, visualization and meta-analysis tools.

Increase your chances for clinical success

MetaBase can provide a trusted source of the basic target and disease biology understanding that AstraZeneca’s study found essential. The solution consists of a vast collection of molecular Interactions (see sidebar), and a detailed map which effectively shows how pairs of molecules interact with each other in various biological chain reactions, or pathways.

For an interaction to be useful a researcher needs to understand three things:

• What is affecting what (direction);
• How one molecule affects the other (mechanism); and
• What happens as a result (effect).

MetaBase is the only database on the market to possess all three of these for all interactions. Without all three the ability to interpret results, but also use the content computationally, is very limited.

Genestack is a unique ecosystem that can evolve with users as their drug discovery research fluxes. Bringing in new data sources, new analysis tools, additional visualization methods, with the ability to share and collaborate on analysis with colleagues in the same department, organization or further will contribute to speeding up drug discovery research and ultimately help improve the clinical success of new drugs or drug targets. Discovery scientists can capitalize on having public and private data resources that are easily findable, accessible, interoperable and reusable (FAIR principles) removing the technical complexities and reducing routine tasks so scientists can focus on making accurate and actionable decisions from their analysis.

A powerful combination

The MetaBase-Genestack combination is a powerful one.

Genestack integrates MetaBase into the existing pipelines within its platform. This empowers all Genestack users consistently to discover and exploit this high-quality resource for all their datasets and analysis. The utility of MetaBase doesn’t end there: Each MetaBase analysis stays on the Genestack platform and can easily be compared or aggregated across different studies, growing scientists’ knowledge base with efficiency and effectiveness that’s not possible elsewhere.

Building an ecosystem within the Genestack platform and bringing in additional tools such as Clarivate's MetaBase pathways database expands the capabilities of both systems. Genestack can provide the data management infrastructure to easily bring together different gene expressions data sources for scientists to interrogate using Clarivate's MetaBase gene signature collections and provide visualization of the pathways.

Many companies also are challenged with data that is often in different formats with little standardization in associated metadata. Genestack can work with clients to pull together MetaBase and all other data regardless of location and format, assist with curation and metadata standardization to make it easily available for scientists to find the data for analysis.

Bringing the two solutions together, MetaBase and Genestack, enhances the power of analysis for scientists to do their work. 

MetaBase content highlights include:

• 1,700,000 molecular interactions.
• More than 1,600 interactive canonical pathway maps capturing nearly 200,000 human, mouse and rat fine metabolic and signaling canonical pathways depicted based on consensus literature findings.
• More than 1 million interactions of proteins with other proteins, DNA, RNA, metabolites and xenobiotics.
• Thousands of putative disease biomarkers.
• More than 750,000 compounds with targets and bioactivity information.
• More than 30,000 metabolic reactions.
• Nearly 8,900 drugs.
• Over 5,300 endogenous metabolites.
• Millions of synonyms resolved for genes, proteins and compounds.
• Protein complexes and protein families resolved in human, mouse and rat.

Genestack key features include:

• Data management: Public and proprietary data of diverse formats are organized and curated using controlled vocabularies and dictionaries for mapping. Indexed data is used in powerful meta-analysis searches to ensure data is findable, accessible, interoperable and reusable.
• Security: The Genestack platform is ISO 27001 compliant and enables compliance with a number of other regulatory standards.
• Access: User controlled permission based data access, including data sharing both within and across organizations.
• File provenance: Transparent workflows and full analysis tracking, aiding data reproducibility and collaboration.
• Integration: Genestack is flexible and modular in nature and can integrate with existing systems such as LIMS or third-party data analysis tools.
• Pipelines and visualization tools: Analyze data using a wide range of customizable tools and pipelines for processing WGS, WES, RNA-seq, microarray data and more.
• Top choice for consumer goods and pharmaceutical R&D organizations

Reference

(1) Cook, David; Brown, Dearg; Alexander, Robert; March, Ruth; Morgan, Paul; Satterthwaite, Gemma; and Pangalos, Menelas N. 2014. Lessons learned from the fate of AstraZeneca’s drug pipeline: A five-dimensional framework. Nature Reviews: Drug Discovery 13: 419–431