Association analysis of the perturbation of interactions in biological pathways and anticancer drug activity

Biochemical and Biophysical Research Communications
Junehawk Lee, Doheon Lee

Abstract

Understanding how different genomic mutational landscapes in patients with cancer lead to different responses to anticancer drugs is an important challenge for realizing precision medicine for cancer. Many studies have analyzed the comprehensive anticancer drug-response profiles and genomic profiles of cancer cell lines to identify the relationship between the anticancer drug response and genomic alternations. However, few studies have focused on interpreting these profiles with a network perspective. In this work, we analyzed genomic alterations in cancer cell lines by considering which interactions in the signaling pathway were perturbed by mutations. With our interaction-centric approach, we identified novel interaction/drug response associations for two drugs (afatinib and ixabepilone) for which no gene-centric association could be found. When we compared the performance of classifiers for predicting the responses to 164 drugs, the classifiers trained with interaction-centric features outperformed the classifiers trained with gene-centric features, despite the smaller number of features (p-value = 2.0 × 10(-3)). By incorporating the interaction information from signaling pathways, we revealed associations between genomic al...Continue Reading

References

Apr 22, 2005·Biological Chemistry·Klaudia Giehl
Nov 8, 2008·Nucleic Acids Research·T S Keshava PrasadAkhilesh Pandey
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Jan 30, 2010·Nature Methods·Gunes GundemNuria Lopez-Bigas
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Jul 6, 2011·Nucleic Acids Research·Boris RevaChris Sander
Jun 6, 2012·The New England Journal of Medicine·Keith T FlahertyUNKNOWN METRIC Study Group
Feb 28, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Federica CatalanottiPaul B Chapman
Mar 15, 2013·Scientific Reports·Rahul KumarGajendra P S Raghava
Sep 26, 2013·Nature Reviews. Cancer·Caitriona HolohanPatrick G Johnston
Oct 2, 2013·Nucleic Acids Research·Roberto MoscaPatrick Aloy
Nov 8, 2013·Nature Reviews. Genetics·Colm J RyanNevan J Krogan
Nov 10, 2013·Nucleic Acids Research·Vivian LawDavid S Wishart
Nov 12, 2013·Nucleic Acids Research·Minoru KanehisaMao Tanabe
Nov 30, 2013·Nucleic Acids Research·Robert D FinnMarco Punta
Dec 4, 2013·Nucleic Acids Research·Robert D FinnAlex Bateman

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.