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Koytiger, G.

Publications and source records attributed to Koytiger, G..

2 recordsLinked to original sources

Generative genomics accurately predicts future experimental results

Realizing AIs promise to accelerate biomedical research requires AI models that are both accurate and sufficiently flexible to capture the diversity of real-life experiments. Here, we describe a generative genomics framework for AI-based experimental prediction that mirrors the process of designing and conducting an experiment in the lab or clinic. We created GEM-1 (Generate Expression Model-1), an AI system that effectively models the enormous range of bulk and single-cell gene expression experiments performed by scientists and benchmarked its performance across multiple biological axes. GEM-1s prediction of future gene expression experiments-RNA-seq data deposited in public archives after our training data cutoff-yielded accuracy comparable to the best-possible performance estimated by comparing the results of matched lab experiments. Overall, our approach illustrates the transformative potential of generative genomics for applications ranging from predicting cellular perturbations in vitro to de novo generation of data from large clinical cohorts.

genomics↗

Crowdsourced mapping of unexplored target space of kinase inhibitors

Despite decades of intensive search for compounds that modulate the activity of particular targets, there are currently small-molecules available only for a small proportion of the human proteome. Effective approaches are therefore required to map the massive space of unexplored compound-target interactions for novel and potent activities. Here, we carried out a crowdsourced benchmarking of predictive models for kinase inhibitor potencies across multiple kinase families using unpublished bioactivity data. The top-performing predictions were based on kernel learning, gradient boosting and deep learning, and their ensemble resulted in predictive accuracy exceeding that of kinase activity assays. We then made new experiments based on the model predictions, which further improved the accuracy of experimental mapping efforts and identified unexpected potencies even for under-studied kinases. The open-source algorithms together with the novel bioactivities between 95 compounds and 295 kinases provide a resource for benchmarking new prediction algorithms and for extending the druggable kinome.

biochemistry↗