Data integration to prioritize drugs using genomics and curated data

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Louhimo , R I , Laakso , M , Belitskin , D , Klefstrom , J , Lehtonen , R & Hautaniemi , S 2016 , ' Data integration to prioritize drugs using genomics and curated data ' , BioData mining , vol. 9 , 21 . https://doi.org/10.1186/s13040-016-0097-1

Title: Data integration to prioritize drugs using genomics and curated data
Author: Louhimo, Riku i; Laakso, Marko; Belitskin, Denis; Klefstrom, Juha; Lehtonen, Rainer; Hautaniemi, Sampsa
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
Date: 2016-05-26
Language: eng
Number of pages: 13
Belongs to series: BioData mining
ISSN: 1756-0381
URI: http://hdl.handle.net/10138/164628
Abstract: Background: Genomic alterations affecting drug target proteins occur in several tumor types and are prime candidates for patient-specific tailored treatments. Increasingly, patients likely to benefit from targeted cancer therapy are selected based on molecular alterations. The selection of a precision therapy benefiting most patients is challenging but can be enhanced with integration of multiple types of molecular data. Data integration approaches for drug prioritization have successfully integrated diverse molecular data but do not take full advantage of existing data and literature. Results: We have built a knowledge-base which connects data from public databases with molecular results from over 2200 tumors, signaling pathways and drug-target databases. Moreover, we have developed a data mining algorithm to effectively utilize this heterogeneous knowledge-base. Our algorithm is designed to facilitate retargeting of existing drugs by stratifying samples and prioritizing drug targets. We analyzed 797 primary tumors from The Cancer Genome Atlas breast and ovarian cancer cohorts using our framework. FGFR, CDK and HER2 inhibitors were prioritized in breast and ovarian data sets. Estrogen receptor positive breast tumors showed potential sensitivity to targeted inhibitors of FGFR due to activation of FGFR3. Conclusions: Our results suggest that computational sample stratification selects potentially sensitive samples for targeted therapies and can aid in precision medicine drug repositioning. Source code is available from http://csblcanges.fimm.fi/GOPredict/.
Subject: Data integration
Drug prioritization
Gene ontology
Cancer
Breast cancer
GENE-EXPRESSION PATTERNS
BREAST-CANCER CELLS
COPY-NUMBER
KINASE INHIBITORS
CLINICAL-PRACTICE
THERAPY
MEDICINE
PATHWAY
TRASTUZUMAB
RESISTANCE
3111 Biomedicine
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