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OTAR Talks (GO Causal Activity Models
Paul D Thomas (GO consortium: aim…
OTAR Talks
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ND: chromatin-related diseases
- Matt Hurl - Sanger (Sebastian Gerety)
- Manos - Cam
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Experiment design: Making genetic modifications in WT cells to transform them into ND and then perform perturbations.
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Carl Anderson: IBD GWAS to drugs using eQTL data
- Have identified novel loci for IBD phenotype
- Aim is to create an eQTL map by single cell RNA seq from gut biopsies from healthy vs Crohn's disease
- There are several types of cells in the gut.
- Mature epithelial cells are hard to culture because they are programmed to apoptose when they lose contact with other cells
- When cells are stressed the gene transcription profile between cytosol and mitochondria are different.
- Single cell eQTL analysis
- Using Conda & Docker to facilitate different environments
- Using nextFlow to consider a workflow approach
- Hashing cells is a technique where cells are tagged with bar coded antibodies that can be read later.
Lisa Dwane (Sanger): ENCORE
- Oncology focused project to identify combination therapies in tumours with unmet clinical need.
- 2G-CRISPR screen: knock out 2 genes and study tumour.
- KRAS-mutant colorectal cancer and triple negative breast cancer have unmet clinical needs.
- Dual KO CRISPR technology is novel here.
- Selection for genes to be deleted: is the gene modified in disease, is the pathway belongs to altered CRC, is the FDA approved drug/preclinical compound, gene expression, core fitness of the gene.
Syed Rzgar (EBI): computational biology
- gene prioritization
- Sources: OTAR, papers,tractability groups (ChEMBL,DrugEBIlity)
Ian Dunham: OTAR update
- Goal is to get from the target to the drug systematically, safely and by integrating existing and new data.
- Have performed a grand CRISPR screen experiment on 300 cancer cell lines in 2019.
- Genetics portal for co-localization - eQTL catalogue, GWAS catalogue
- Aim for 2020 is to explore value from OTAR and promoting this.
- Value: creating informatics value by integrating the genetics portal.
- Value: Network analysis from IntAct aiming for target expansion.
- Value: Ongoing project in genetics portal to go from locus to gene.
- Value: Ongoing project that aims for cell-specific SNPs.
- The three segments in OTAR are Platform, Genetics and Validation Lab.
- New projects on validating targets.
- Project: Cell specific and single cell network analysis for target identification.
- Project: Identify causal cellular processes from BioBanks and other resources to enable genetic response modelling.
- Intranet page: http://home.opentargets.org/
Panos Zalmas: Experimental validation
- Aim to validate targets emerging from computational work in the team.
- Targets have a high attrition rate.
- High throughput experiments may harbour unexplored targets.
- Results may result in identifying various aspects for the target - phenotype, kinetic parameters, etc.
EVA - Kirill Tsukanov
- EVA/ClinVar/OT collaboration
- EVA gets data from ClinVar and massages the data
- ClinVar data cannot always be mapped to specific genes and diseases
- no terms
- non-standardised terms
- repeat expansion variants
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