#AGBTPH – Nicolas Robine, NYGC glioblastoma clinical outcome study: Discovering therapeutic potential in GBM through integrative genomics.

Nicolas Robine, New York Genome Center  (@NotSoJunkDNA)

Collaborate with IBM to study Glioblastoma.

Big workup: Tumour normal WGS, tumour RNA-Seq, methylation array.

Pipeline: FASTQ, BAM, 3 callers each for {SNV, INDEl, SV}.  Rna-Sea uses fusionCatcher, Star-Fusion, Alignment with STAR.

It’s hard to do tumour normal comparison, so you need to get estimation of genes baseline.  Use TCGA RNA-Seq as background so you can compare.  Z-score normalization was suspicious, which correspond to regions of high-GC content.  Used EDASeq to do normalization, batch-effect correction with Combat.  Z-scores change over the course of the study, which is uncomfortable for clinicians.

Interpretation: 20h FTE/Sample.   Very time consuming with lots of steps, cumulating with a clinical report delivered to the referring physician.  Use Watson for Genomics to help.  Oncoprint created as well.

Case study presented: Very nice example of evidence, with variants found, RNA-seq used to identify complimentary deletion events, which cumulated in the patient being enrolled in a clinical trial.

Watson was fed same data – solved the issue in 9 minutes!  (Recommendations were slightly different, but same issues found.)  If the same sample is given to two different people, the same issue arrises.  It’s not perfect, but it’s not completely crazy either.

Note: don’t go cheap!  Sequence the normal sample.

[Wow]: 2/3rd of recommendations were done based on CNVs.

Now in second phase, with 200 cases, any cancer type.  29 cases complete.

What was learned:  identify novel variants in most samples, big differences between gene panel testing and WGS.  built a great infrastructure, and Watson for Genomics can be a great resource for scaling this.

More work needed, incorporating more data – and more data needed about the biology – and more drugs!

[Dring questions – First project: 30 recommendations, zero got the drugs. Patient are all at advanced phases of cancer, and has been difficult to convince doctor to start new therapies.  Better response with new project.]

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