Join us for this seminar by Ava Khamseh (Edinburgh) as part of the Maths in the Life Sciences seminar series here in Manchester (and the online North West Seminar Series in Mathematical Biology and Data Sciences in collaboration with Liverpool Universities).
Title: Pinpointing cell (sub)types, states and transcription factor mechanisms via quantification of (high order) molecular dependencies
Abstract: The genome contains the complete set of DNA that provides instructions for cells and tissues to develop and function. Genomic medicine integrates insights from the genome with information about a person’s health to design and apply improved diagnostic tools and treatments. Research in genomic medicine goes beyond identification of risk factors and aims at pinpointing underlying causal mechanisms, often at various biological scales.
In the first part of this talk, we introduce Stator, a data-driven methodology that identifies cell (sub)types and states without relying on cells’ local proximity in transcriptome space, in contrast to methods such as clustering. Stator labels the same single cell multiply, not just by type and sub-type, but also by state such as activation, maturity or cell cycle sub-phase, through deriving higher-order (beyond pair-wise) gene expression dependencies from a sparse gene-by-cell expression matrix. We exemplify Stator in liver disease/cancer to reveal expression programmes that identify early cancer states and predict patient survival.
In the second part of the talk, we present a novel approach, integrating population genetics, functional genomics and targeted machine learning (TarGene), to quantify epistatic contributions to human traits via transcription factor mechanisms. By taking experimentally verified differentially binding variants across 9 nuclear hormone receptors as candidates and using UK Biobank data across 768 traits, we reveal, for the first time, hundreds of epistatic interactions involving these transcription factor mechanisms.
The talk will be also be streamed via Teams, please contact carl.whitfield@manchester.ac.uk or igor.chernyavsky@manchester.ac.uk for the zoom link, or sign up to the mailing list.
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