Extracting biological features from ‘big data’ with ADAGE – Dr. Casey Greene

Dr. Casey Greene, University of Pennsylvania – talk at UC Davis, October 12, 2015

Twitter, to be used! @GreeneScientist

Started with example that Carrots are routine fun part of every day! Just like bioinformatics and genomics. Aim to scale up data universe from lab -> publicly-available -> compendium. Big data universe right now includes all the data collected, really big for humans available now ~1.3 million public assays. Can we use?

2015-10-12_11-10-47

Analysis methods are accessible, available, affordable. Sustainable for compendium of human data  and also nonmodel systems.

Worlds fastest introduction to machine learning. Classes of algorithms. What patterns normally exist? Unsupervised algorithm vs. supervised giving system some knowledge. With new data, what else looks like it? What new features can you extract that I care about?

Example with tissue-specific expression from cell lineages. Physically too connected to each other. COmputationlly, wanted to subtract out what not interested in. Started with large data sets, small set of genes curated from literature that interested. Machine learning approach. List of genes specifically expressed for cell lineage.

Support vector machines (not a scary method, despite name!): Expression of features in sample 1, low expression of same features in sample 2 and other features high in both. Place line in manner to maximally separate data from different animals, support vectors will create buffered area + and – surrounding the line.

In silico predictions, now that I know where proteins are expressed, what other information can we learn?

Functional interaction standard, genes work together during specific processes. Assumption that functioning together in tissues. Structure algorithm to use this and make predictions from this assumption. Draw gold standard of things you think will work together by overlaying tissue on process network. Judge every publicly-available by how much it tells you about that tissues. Generate network for every tissue and do things like understand how genes are connected to each other, disease states, GWAS.

Take a look at Greene et al. Nature Genetics, 2015.

GWAS example: Cases vs. Controls, Manhattan plot for every SNP in genome. Low statistical strength because of low-frequency mutations. Don’t observe enough to draw strong inference, possibly small effects. Noisy data. Build prediction, then better mapping to annotated disease genes. For example, Kidney NetWAS of hypertension. Also, lupus Type 2 Diabetes, etc. (Irene’s paper just accepted)

Discovery is the point. “Research is to see what everyone else has seen, to think what nobody else has thought.” -Albert Szent-Györgyi

Should be using unsupervised algorithms from a discovery standpoint. If you showed 16,000 computers 10 million images from youtube, what would they see?

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Cats. Le et al. 2012 Unsupervised discovery for Google.

Analysis with Denoising Autoencoders of Gene Expression (ADAGE), preprint:

Jie Tan, John H Hammond, Deborah A Hogan, Casey S Greene. 2015. ADAGE analysis of publicly available gene expression data collections illuminates Pseudomonas aeruginosa-host interactions. doi: http://dx.doi.org/10.1101/030650

Judge algorithm for how well it removes noise.

Gene Expression -> add random noise -> corrupted expression -> extract features -> interpret -> biological meaning, e.g. growth rate, strain, oxygen, then reconstruct Gene Expression.

Tan et al. Pac Symp Biocomput. 2015:132-43.

Corroborating evidence from LeCun Bengio and Hund Nature 2015  that unsupervised learning has something going for it.

Generate meaningful hyptheses…produce useful networks.

ADAGE identifies strain differences. Genome Hybridization, PA01 vs. PA14. Activity value of one node, low to high activitiy. If I care about strains, things that don’t hyb will look different. Algorithm can differentiate. Confirmation that model is pulling out biological properties.

ADAGE-based pathway analysis of transcriptomic changes, e.g. regulators of nitrogen metabolism. Gives us smaller universe to think about, looking at processes as a whole. Lets us get beyond curated pathway database, e.g. KEGG. This is really, really, really cool. (example that you will only get 1 gene if you relied on curated KEGG database, relative to network discovery from ADAGE)

Pan-Cancer Analysis with tissue biopsies.

PILGRM is for biologists: Greene and Tryoanskaya Nucleic Acids Research. 2011

Wong et al. Nucleic Acids Res. 2012

Tribe, Zelaya and Green, In prep

Sign up on webpage to get info on web servers:

http://www.greenelab.com/webservers/

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About Lisa Cohen

PhD student at UC Davis.
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