Evaluation of gene-drug common module identification methods using pharmacogenomics data.

Abstract:

:Accurately identifying the interactions between genomic factors and the response of cancer drugs plays important roles in drug discovery, drug repositioning and cancer treatment. A number of studies revealed that interactions between genes and drugs were 'many-genes-to-many drugs' interactions, i.e. common modules, opposed to 'one-gene-to-one-drug' interactions. Such modules fully explain the interactions between complex biological regulatory mechanisms and cancer drugs. However, strategies for effectively and robustly identifying the underlying common modules among pharmacogenomics data remain to be improved. In this paper, we aim to provide a detailed evaluation of three categories of state-of-the-art common module identification techniques from a machine learning perspective, including non-negative matrix factorization (NMF), partial least squares (PLS) and network analyses. We first evaluate the performance of six methods, namely SNMNMF, NetNMF, SNPLS, O2PLS, NSBM and HOGMMNC, using two series of simulated data sets with different noise levels and outlier ratios. Then, we conduct experiments using a real world data set of 2091 genes and 101 drugs in 392 cancer cell lines and compare the real experimental results from the aspect of biological process term enrichment, gene-drug and drug-drug interactions. Finally, we present interesting findings from our evaluation study and discuss the advantages and drawbacks of each method. Supplementary information: Supplementary file is available at Briefings in Bioinformatics online.

journal_name

Brief Bioinform

authors

Huang J,Chen J,Zhang B,Zhu L,Cai H

doi

10.1093/bib/bbaa087

subject

Has Abstract

pub_date

2020-06-26 00:00:00

eissn

1467-5463

issn

1477-4054

pii

5860683

pub_type

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