Omic statistical learning with Next-Generation Data!

Project Workflow

Curate Genomic, Transcriptomic, and Metabolomic data from Depmap (depmap.org)

Collect methionine dependency labels for cell lines in lab

Put training and validation data through Keras API

Predict methionine dependency in test cells

Extract feature (gene) importance

Feature (genetic) manipulation with CRISPR to change methionine dependent phenotype!

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How will deep learning help?

Neural Networks are perfect for classification problems with a lot of features, and methionine dependency is a binary classification problem!

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Data Augmentation

There are only 40 cell lines with clearly characterized methionine dependency. How do we overcome the limitation of the insufficient observations?

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Transcription factor binding motif and Convolutional Neural Networks

One hot encode ATCG to [1,0,0,0], [0,1,0,0]....

Set up CNN with Keras

Ask CNN: What are the important bases?

Is this technique transferable to protein and RNA motif deep learning?

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Metabolite Levels in Cells

Is methionine dependency related to metabolite levels in the cells?

These 40 cell lines are clustered in a way that the cell before SKCO1 is dependent of methionine and the cell after A172 is independent of methionine! Do you see a pattern? Note that the dependent cells do not have abnormal methionine, homocysteine, and S-adenosylhomocysteine levels!

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Metabolite vs. Gene Dependency

How do metabolites affect gene dependency? Zoom in on the plot and check it out! Notice that Asparagine levels are highly correlated with ASNS (Asparagine Synthase) dependency!

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Gene Expression Levels and Methionine Dependency

Is there a difference in gene expression levels between methionine dependent and independent cells?

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