Robust drug target selection

Identifying a robust target (most of which are proteins) that plays a major causal role in the disease in focus is a critical early milestone for any therapeutic development program, where a mistake at this stage could be disastrous and costly. Understanding whether phenotype/protein expression associations represent a cause or consequence of disease is far from trivial in human clinical studies, but the unique advantages of combining genomics and proteomics data (“proteogenomics”) can provide unique insights into the likely causal roles of any given protein in a specific disease.

pQTLs - a vital proteogenomic tool for drug target discovery

Researchers are now using protein quantitative trait loci (pQTLs) to link genetic variation, proteins, and disease. pQTLs are locations in the genome that contain one or more genetic variants associated with circulating protein levels. Genetic variants that are close to, or within the same gene that makes the protein are called cis-pQTLs, and those that are in a different location, and therefore indirectly affect the protein-making gene, are called trans-pQTLs (see figure below).

When cis-pQTL data is combined with phenotypic data in a Mendelian Randomization (MR) analysis, it provides extremely strong evidence that the protein plays a causal role in the disease or biological process being studied, which is critically important for reliable drug target identification.
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When cis-pQTL data is combined with phenotypic data in a Mendelian Randomization (MR) analysis, it provides extremely strong evidence that the protein plays a causal role in the disease or biological process being studied.

This powerful approach is being rapidly adopted by the scientific community and has also resulted in a major international consortium dedicated to large-scale collaboration and pQTL data sharing. SCALLOP is an independent collaborative framework for the discovery and follow-up of genetic associations with proteins for researchers generating data using the Olink platform. The aim of the SCALLOP consortium is to identify novel molecular connections and protein biomarkers that are causal in diseases, and to date, 35 PIs from 28 research institutions have joined the effort, which now comprises summary level data for almost 70,000 patients and controls from 45 cohort studies.

		In a podcast with Drug Discovery News, Dr. Anders Mälarstig, Director of Human Genetics at Pfizer, explains pQTLs in more detail, and how they benefit the drug development process. Listen to the podcast

In a podcast with Drug Discovery News, Dr. Anders Mälarstig, Director of Human Genetics at Pfizer, explains pQTLs in more detail, and how they benefit the drug development process.

Listen to the podcast

SCALLOP (2) — Mendelian Randomization combining genomics and proteomics data to identify potential new drug targets.

Population scale proteomics accelerates the search for effective new drug targets

Dr. Chris Whelan (Chair and Principal Investigator of the UK Biobank – Pharma Proteomics Project) discusses how data from the UK Biobank – Pharma Proteomics Project has revealed new insights into associations between gene variants and protein concentrations enabling new causal biomarkers for diseases to be identified as well as new drug targets with higher probabilities of success.

Proteomics helps provide a much needed layer of resolution to genetic data. Genomics is the beautiful, reliable but slightly ageing car – proteomics might serve as the new engine

Dr. Chris Whelan

Empowering genomics with proteomics

A new white paper describes how the integration of genomics and proteomics data heralds a new era of discovery. Data from the landmark UK Biobank – Pharma Proteomics Project, as well as the SCALLOP consortium have identified many new associations between genetic variants and circulating protein levels. The article discusses how such population-scale proteogenomic projects are delivering a wealth of actionable data to drive future drug development.

Download the white paper

Therapeutic Targets for Heart Failure Identified With Plasma Proteome and Genome Analysis

This study may not only inform new heart failure treatments, wrote the authors of the analysis, but their methods can provide a roadmap for discovering drug targets in other diseases using proteomic and genomic data.

Download the article

Get more information about SCALLOP and see a brief video interview with the consortium founder, Dr. Anders Mälarstig (Pfizer & Karolinska Institute).

The SCALLOP Consortium

Proteomics can complement genomics to identify new regulatory pathways, biomarkers, and drug targets, according to a panel of proteogenomics experts.

Read the article

Robust drug target selection

pQTLs - a vital proteogenomic tool for drug target discovery

Read more

When cis-pQTL data is combined with phenotypic data in a Mendelian Randomization (MR) analysis, it provides extremely strong evidence that the protein plays a causal role in the disease or biological process being studied.

Proteomics helps provide a much needed layer of resolution to genetic data. Genomics is the beautiful, reliable but slightly ageing car – proteomics might serve as the new engine

Proteomics at the heart of multiomics strategies

Hear from industry experts on how proteomics is changing the way we develop new drugs and study disease.

The power of proteomics in multiomic studies