Genomic data integration by WON-PARAFAC identifies interpretable factors for predicting drug-sensitivity in vivo.

Genomic data integration by WON-PARAFAC identifies interpretable factors for predicting drug-sensitivity in vivo.

Publication date: Nov 06, 2019

Integrative analyses that summarize and link molecular data to treatment sensitivity are crucial to capture the biological complexity which is essential to further precision medicine. We introduce Weighted Orthogonal Nonnegative parallel factor analysis (WON-PARAFAC), a data integration method that identifies sparse and interpretable factors. WON-PARAFAC summarizes the GDSC1000 cell line compendium in 130 factors. We interpret the factors based on their association with recurrent molecular alterations, pathway enrichment, cancer type, and drug-response. Crucially, the cell line derived factors capture the majority of the relevant biological variation in Patient-Derived Xenograft (PDX) models, strongly suggesting our factors capture invariant and generalizable aspects of cancer biology. Furthermore, drug response in cell lines is better and more consistently translated to PDXs using factor-based predictors as compared to raw feature-based predictors. WON-PARAFAC efficiently summarizes and integrates multiway high-dimensional genomic data and enhances translatability of drug response prediction from cell lines to patient-derived xenografts.

Open Access PDF

Kim, Y., Bismeijer, T., Zwart, W., Wessels, L.F.A., and Vis, D.J. Genomic data integration by WON-PARAFAC identifies interpretable factors for predicting drug-sensitivity in vivo. 05727. 2019 Nat Commun (10):1.

Concepts Keywords
Invariant Precision medicine
Nonnegative G factor
Precision Medicine Xenotransplantation
Vivo Patient derived xenograft
Xenograft Cancer research
Xenografts Branches of biology
Medical specialties
Medicine

Semantics

Type Source Name
gene UNIPROT GOPC
disease MESH multi
gene UNIPROT CISH
gene UNIPROT LARGE1
drug DRUGBANK Coenzyme M
drug DRUGBANK Tropicamide
drug DRUGBANK Pralatrexate
disease DOID cancer
disease MESH cancer
gene UNIPROT DEPP1
gene UNIPROT INPP5D
gene UNIPROT CDKN2A
gene UNIPROT CDKN2B
gene UNIPROT ASAP1
gene UNIPROT PTK2
gene UNIPROT PTEN
gene UNIPROT RB1
gene UNIPROT SLC6A2
gene UNIPROT EPHB1
gene UNIPROT ELK3
disease MESH mesothelioma
drug DRUGBANK Natural alpha interferon
gene UNIPROT CDK4
drug DRUGBANK Palbociclib
gene UNIPROT ERBB2
gene UNIPROT EGFR
gene UNIPROT MTOR
drug DRUGBANK Afatinib
disease MESH glioma
pathway BSID Glioma
pathway BSID Insulin Signaling
pathway BSID Oxidative phosphorylation
pathway BSID Glycolysis
pathway BSID glycolysis
drug DRUGBANK ATP
gene UNIPROT PPP3CA
gene UNIPROT BFAR
gene UNIPROT NR1H4
drug DRUGBANK Piroxicam
gene UNIPROT AGRP
gene UNIPROT TOP1
drug DRUGBANK Camptothecin
drug DRUGBANK Irinotecan
disease MESH separated
gene UNIPROT MST1R
pathway BSID mTOR signaling pathway
pathway BSID MAPK Signaling Pathway
pathway BSID MAPK signaling pathway
drug DRUGBANK Flunarizine
gene UNIPROT FRZB
pathway BSID Notch signaling
gene UNIPROT FANCC
gene UNIPROT FUT1
gene UNIPROT CCAR1
gene UNIPROT TP53
pathway BSID Apoptosis
drug DRUGBANK Ubiquinol
pathway BSID Adipogenesis
drug DRUGBANK L-Asparagine
gene UNIPROT TCF7
gene UNIPROT ITK
gene UNIPROT PRKCQ
gene UNIPROT GRAP2
gene UNIPROT EPHB6
gene UNIPROT LCK
gene UNIPROT LEF1
gene UNIPROT HHIP
gene UNIPROT IFNG
gene UNIPROT HDAC11
gene UNIPROT TGFB3
gene UNIPROT ESR1
gene UNIPROT FGFR4
gene UNIPROT STK16
gene UNIPROT SESN2
gene UNIPROT CARS
gene UNIPROT KDM4A
gene UNIPROT BBC3
gene UNIPROT KRT20
gene UNIPROT BCL2L14
gene UNIPROT GUCY2C
gene UNIPROT NOSTRIN
gene UNIPROT AXIN2
gene UNIPROT PIP5K1B
gene UNIPROT TSPAN8
gene UNIPROT SPINK1
gene UNIPROT HNF1A
gene UNIPROT IK
disease MESH leukemia
disease DOID leukemia
disease MESH T cell leukemia
pathway BSID p53 pathway
disease MESH breast cancer
disease DOID breast cancer
pathway BSID Breast cancer
disease MESH growth
pathway BSID Translation
disease MESH ductal carcinoma
disease MESH carcinoma
disease DOID carcinoma
disease MESH melanoma
disease DOID melanoma
pathway BSID Melanoma
drug DRUGBANK Encorafenib
drug DRUGBANK Trastuzumab
drug DRUGBANK Binimetinib
disease DOID NSCLC
gene UNIPROT AICDA
disease DOID cutaneous melanoma
gene UNIPROT AOC2
gene UNIPROT TNFRSF19
gene UNIPROT BTG3
disease MESH colon cancers
gene UNIPROT SCN8A
gene UNIPROT APPL1
gene UNIPROT SOAT1
gene UNIPROT LAT2
gene UNIPROT PROC
disease MESH ovarian cancer
disease DOID ovarian cancer
disease MESH colorectal cancers
gene UNIPROT LITAF
gene UNIPROT PACC1
disease DOID Malignant Pleural Mesothelioma
pathway BSID Metabolism
disease MESH tumorigenesis
disease MESH Death
gene UNIPROT STAT2
disease MESH malignant lymphoma
disease DOID acute leukemia
disease MESH Hematological Malignancies
gene UNIPROT GAN
disease DOID colorectal cancer
pathway BSID Colorectal cancer
drug DRUGBANK Topotecan
gene UNIPROT CASP8
drug DRUGBANK Gemcitabine
disease MESH adenocarcinoma
disease DOID adenocarcinoma
gene UNIPROT NRAS
gene UNIPROT TNIP1
disease DOID face
gene UNIPROT ELOVL6
gene UNIPROT FANCE
gene UNIPROT LRRC15
disease MESH Bas
gene UNIPROT RXFP2
pathway BSID Reproduction

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