Cancer Genomics: Integrative and Scalable Solutions

in R/Bioconductor

Year 1 renewal update

Levi Waldron, Martin Morgan (co-PIs)Vincent Carey, Davide Risso (co-investigators)

May 27, 2020

@leviwaldron1

NCI ITCR #5U24CA180996

Infrastructure for analysis of multimodal data

• Parent grant (completed August 2019)– MultiAssayExperiment and data resources– RaggedExperiment– Form a basis for much of the multimodal data

analysis in Bioconductor

• Renewal grant– Extensions to single-cell multimodal data– Leveraging Bioconductor for variant prioritization– Performant computing and education

MultiAssayExperimentDeveloped during parent grant

Credit: Marcel Ramos

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Ramos M, Schiffer L, Re A, Azhar R, Basunia A, Rodriguez C, Chan T, Chapman P, Davis SR, Gomez-Cabrero D, Culhane AC, Haibe-Kains B, Hansen KD, Kodali H, Louis MS, Mer AS, Riester M, Morgan M, Carey V, Waldron L: Software for the Integration of Multiomics Experiments in Bioconductor. Cancer Res. 2017, 77:e39–e42.

Depended / Imported / Suggestedby 32 Bioconductor packages

cBioPortalDataWebinar on cBioPortal API & R ClientThursday May 28th 11am – 12pm EDT

by Ino de Bruijnhttps://www.cbioportal.org/tutorials

Under Reviewhttps://github.com/link-ny/curatedTCGAManu

cBioPortalData + curatedTCGAData

Under Reviewhttps://github.com/link-ny/curatedTCGAManu

Webinar on cBioPortal API & R ClientThursday May 28th 11am – 12pm EDT

by Ino de Bruijnhttps://www.cbioportal.org/tutorials

Data resources (released this year)

1. cBioPortalData + curatedTCGAData– collaboration with cBioPortal

2. MultiModalData– single-cell multimodal benchmark datasets

3. curatedMetagenomicData1, HMP16SData2

– Multi’omic data for human microbiome studies

1Pasolli E, Schiffer L, Manghi P, Renson A, Obenchain V, Truong DT, Beghini F, Malik F, Ramos M, Dowd JB, Huttenhower C, Morgan M, Segata N, Waldron L: Accessible, curated metagenomic data through ExperimentHub. Nat. Methods 2017, 14:1023–1024.

2Schiffer L, Azhar R, Shepherd L, Ramos M, Geistlinger L, Huttenhower C, Dowd JB, Segata N, Waldron L: HMP16SData: Efficient Access to the Human Microbiome Project Through Bioconductor. Am. J. Epidemiol. 2019, 188:1023–1026.

New softwareCNVRanger: population CNV analysis

da Silva V, Ramos M, Groenen M, Crooijmans R, Johansson A, Regitano L, Coutinho L, Zimmer R, Waldron L, Geistlinger L: CNVRanger: association analysis of CNVs with gene expression and quantitative phenotypes. Bioinformatics 2019.

New workflowTumor-only allele-specific CNV analysis

from clinical exome sequencing

Oh S, Geistlinger L, Ramos M, Morgan M, Waldron L, Riester M: Reliable Analysis of Clinical Tumor-Only Whole-Exome Sequencing Data. JCO Clin Cancer Inform 2020, 4:321–335.

AnVIL NHGRI collaboration

Oh S, Geistlinger L, Ramos M, Morgan M, Waldron L, Riester M: Reliable Analysis of Clinical Tumor-Only Whole-Exome Sequencing Data. JCO Clin Cancer Inform 2020, 4:321–335.

Scalable infrastructure

1. ExperimentHub– Cloud distribution of curated databases

curatedTCGAData, etc2. BiocFileCache– Simplified host file caching

3. DelayedArray– Out-of-memory data representation using HDF5

4. BiocParallel– Simplified parallel evaluation

Bioconductor core team: Martin Morgan, Lori Shepherd, Herve Pages, Valerie Obenchain

MultiAssayExperiment collaboration with other ITCR projects

• cBioPortalData– Expose and make available data from the

cBioPortal web resources

• AMARETTO– Regulatory network inference and driver gene

evaluation using integrative multi-omics analysis and penalized regression

Thank youITCR #5U24CA180996 Collaborators (shortlist)– Martin Morgan, Vincent Carey, Davide Risso– cBioPortal team (esp. Ino de Bruijn)– Lori Shepherd, Nitesh Turaga, Herve Pages, Valerie

Obenchain, …– Marcel Ramos, Ludwig Geistlinger, Sehyun Oh

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