A Second Generation Cancer Dependency Map, Open Targets Gentropy alpha release, scSNV-seq

It’s a new year at Open Targets! Not only that, it’s our 10th anniversary year. Kicking off in March, keep an eye out for celebratory content.

2024 is off to a strong start. In this roundup, we dive into the two papers published by Open Targets teams this month, and we introduce the alpha version of the Open Targets Genetics portable pipelines.

Wracking my brain for tin or aluminium commemorative items (suggestions — and gifts — welcome),

Open Targets

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A Second Generation Cancer Dependency Map

The team at Open Targets, Wellcome Sanger Institute and collaborators annotated 930 cancer cell lines with multiomic data to generate a second-generation map of cancer dependencies — the most comprehensive study of its type.

They identified 370 priority drug targets for 27 cancer types in a truly data-driven approach, leveraging clinical-relevant transcriptional signatures, metabolic and proteomics data, protein-protein interaction networks and more.

Analysing the largest-ever cancer dependency dataset, we present the most comprehensive map yet of human cancers' vulnerabilities — their ‘Achilles heel’. We identify a new list of top-priority targets for potential treatments, along with clues about which patients might benefit the most — all made possible through the design and use of innovative computational and machine intelligence methodologies. — Francesco Iorio, co-lead author of the study.

Reference. Pacini, C et al. A comprehensive clinically informed map of dependencies in cancer cells and framework for target prioritization. Cancer Cell

Introducing scSNV-seq

scSNV-seq is a method to directly link genotype to whole-transcriptome readout in high-throughput single-cell perturbation screens.

scSNV-seq couples single-cell genotyping and transcriptomics of the same cells, which allows for accurate and high-throughput screening of single nucleotide variants (SNVs) such as those deriving from cancer genome sequencing, rare variant analysis or GWAS.

Importantly, the technique allows you to differentiate benign variants or variants with an intermediate phenotype, and does not rely on gRNA identity to infer genotype, so is applicable in a range of screens.

Reference. Cooper, SE., Coelho, MA., Strauss, ME., et al. scSNV-seq: high-throughput phenotyping of single nucleotide variants by coupled single-cell genotyping and transcriptomics. Genome Biology

We have released the Open Targets Genetics Pipelines Alpha (01.24)!

We have re-developed the Open Targets Genetics pipelines wrapped as the Gentropy Python package. These incorporate the first optimised version of the pipelines for genetic data ingestion and harmonisation, as well as the pipelines for clumping, PICS fine-mapping, eCAVIAR colocalisation and L2G-pics calculation.

The Gentropy v.1.0.0 package is available to install via PyPi. Take a look at the documentation.

Check out the Open Targets Community for more information. As this is an alpha release, we are very keen to hear feedback from our users, so please do get in touch if you have any thoughts or suggestions.

We were at the Festival of Genomics! Did you spot us?

Carl Anderson gave a talk describing how he uses single-cell RNA-sequencing to identify genes, pathways and cell types causally driving susceptibility to Inflammatory Bowel Disease, and Helena Cornu presented a poster on the Open Targets consortium.

Job Board

Interested in joining Open Targets? We are currently recruiting:

• Advanced Research Assistant (2 Feb) — join a multidisciplinary project applying single cell genomics to cells isolated from patients with inflammatory bowel disease (IBD) or healthy control patients, which aims to identify genetic variants associated with gene expression in intestinal cells, and combine these with data from genetic studies of IBD patients to identify potential novel drug targets for IBD.
• Executive Administrator (16 Feb) — provide support to Gosia Trynka, who has a dual role as Director of Experimental Sciences at Open Targets and Group Leader in the Human Genetics Programme at the Wellcome Sanger Institute. Note this is a 12-month maternity cover.
• NLP Data Scientist (16 Feb) — join the newly initiated AI knowledge management project as part of the Chemical Biology Services Team. We are in particular interested in applications of AI and machine learning to mine the research literature for additional types of entities relevant to drug discovery not currently available to Open Targets (such as variants, biomarkers, tissues/cell types, adverse events, and assay conditions).
• Postdoctoral Fellow - Mapping E3-Ligase Mediated Protein Degradation in Cancer Cells (18 Feb) — based in the laboratory of Dr. Mathew Garnett, help generate and interpret large-scale proteomic datasets to map E3 target genes.This project will help provide insights into the cellular processes regulating protein degradation in cancer cells with the aim of advancing new therapies modulating protein degradation to selectively target cancer cells.

Keep an eye on our jobs page for all our opportunities.