Determination of minimal transcriptional signatures of compounds for target prediction.

EURASIP Journal on Bioinformatics & Systems Biology
Florian NigschJeremy L Jenkins

Abstract

The identification of molecular target and mechanism of action of compounds is a key hurdle in drug discovery. Multiplexed techniques for bead-based expression profiling allow the measurement of transcriptional signatures of compound-treated cells in high-throughput mode. Such profiles can be used to gain insight into compounds' mode of action and the protein targets they are modulating. Through the proxy of target prediction from such gene signatures we explored important aspects of the use of transcriptional profiles to capture biological variability of perturbed cellular assays. We found that signatures derived from expression data and signatures derived from biological interaction networks performed equally well, and we showed that gene signatures can be optimised using a genetic algorithm. Gene signatures of approximately 128 genes seemed to be most generic, capturing a maximum of the perturbation inflicted on cells through compound treatment. Moreover, we found evidence for oxidative phosphorylation to be one of the most general ways to capture compound perturbation.

References

Feb 13, 2003·Nucleic Acids Research·Rafael A IrizarryTerence P Speed
Feb 13, 2004·Bioinformatics·Laurent GautierRafael A Irizarry
Jul 29, 2004·Drug Discovery Today·Richard MorphyZoran Rankovic
Mar 15, 2005·Nature Biotechnology·Diego di BernardoJames J Collins
Jun 14, 2005·Trends in Biotechnology·R Keira CurtisAntonio Vidal-Puig
Feb 9, 2007·Nature Biotechnology·Michael J KeiserBrian K Shoichet
Jul 16, 2008·Science·Monica CampillosPeer Bork
Dec 4, 2008·Engineering Applications of Artificial Intelligence·Otis SmartGeorge Vachtsevanos
Dec 6, 2008·Journal of Chemical Information and Modeling·Florian NigschJohn B O Mitchell
Feb 11, 2009·Nature Biotechnology·Irene NobeliJanet M Thornton
Aug 18, 2009·Computational Statistics & Data Analysis·Brooke L FridleyKent Bailey
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Francesco IorioDiego di Bernardo
Sep 15, 2010·PLoS Computational Biology·Murat IskarPeer Bork
Oct 12, 2010·Autophagy·Francesco IorioNicola Brunetti-Pierri
Nov 4, 2010·Nucleic Acids Research·Damian SzklarczykChristian von Mering
Nov 10, 2010·Nucleic Acids Research·Craig KnoxDavid S Wishart
Feb 11, 2011·Nature·Aled M EdwardsFrank H Yu
Sep 29, 2011·Nucleic Acids Research·Anna GaultonJohn P Overington
Oct 6, 2011·EURASIP Journal on Bioinformatics & Systems Biology·Dorothea EmigMario Albrecht

❮ Previous
Next ❯

Citations

Oct 20, 2015·Nature Chemical Biology·Anne Mai WassermannMeir Glick
May 18, 2016·Assay and Drug Development Technologies·Hans De WolfHinrich W H Göhlmann
Feb 10, 2017·PLoS Computational Biology·Tracey M FilzenMatthew Tudor
Feb 13, 2014·Journal of Biomolecular Screening·Savina JaegerJeremy L Jenkins

❮ Previous
Next ❯

Methods Mentioned

BETA
chips
protein folding

Software Mentioned

affy
GeneGO Metacore
Connectivity Map
R
Excel
StringDB
cython
Connectivity Map 2 ( CMAP2 )
CUDA
ChEMBL

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.

© 2021 Meta ULC. All rights reserved