Exploring novel mechanistic insights in Alzheimer's disease by assessing reliability of protein interactions

Scientific Reports
Ashutosh MalhotraMartin Hofmann-Apitius

Abstract

Protein interaction networks are widely used in computational biology as a graphical means of representing higher-level systemic functions in a computable form. Although, many algorithms exist that seamlessly collect and measure protein interaction information in network models, they often do not provide novel mechanistic insights using quantitative criteria. Measuring information content and knowledge representation in network models about disease mechanisms becomes crucial particularly when exploring new target candidates in a well-defined functional context of a potential disease mechanism. To this end, we have developed a knowledge-based scoring approach that uses literature-derived protein interaction features to quantify protein interaction confidence. Thereby, we introduce the novel concept of knowledge cliffs, regions of the interaction network where a significant gap between high scoring and low scoring interactions is observed, representing a divide between established and emerging knowledge on disease mechanism. To show the application of this approach, we constructed and assessed reliability of a protein-protein interaction model specific to Alzheimer's disease, which led to screening, and prioritization of four nov...Continue Reading

References

Jun 25, 2003·The Journal of Biological Chemistry·Zhiming SuoBarry W Festoff
Jan 27, 2005·The Journal of Biological Chemistry·Jun Xie, Qing Guo
Jun 18, 2005·Bioinformatics·Haiyan HuXianghong Jasmine Zhou
Sep 13, 2006·The European Journal of Neuroscience·Kiyoko S MurayamaWataru Araki
Jan 27, 2007·BMC Bioinformatics·Suresh MathivananAkhilesh Pandey
Jul 17, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Thomas L HornDavid L McCormick
Jan 10, 2008·Nature Biotechnology·Luke HakesSimon C Lovell
Jul 16, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Arun K GhoshJordan Tang
Jul 25, 2008·The Journal of Biological Chemistry·Sarah L Cole, Robert Vassar
Jul 1, 2010·PLoS Computational Biology·Javier De Las Rivas, Celia Fontanillo
Oct 12, 2010·Apoptosis : an International Journal on Programmed Cell Death·Ashvinder Raina, Deepak Kaul
Nov 4, 2010·Nucleic Acids Research·Damian SzklarczykChristian von Mering
Jul 1, 2011·Nature Methods·Bruno ArandaHenning Hermjakob
Nov 19, 2011·Nucleic Acids Research·Luana LicataGianni Cesareni
Feb 22, 2012·PloS One·Martin H SchaeferMiguel A Andrade-Navarro
Mar 29, 2012·Nature Methods·Sandra OrchardHenning Hermjakob
Dec 20, 2012·BMC Medical Informatics and Decision Making·Erfan YounesiJuliane Fluck
Jul 12, 2013·Drugs & Aging·Genevieve Evin, Christopher Hince
Jan 29, 2014·The Journal of Biological Chemistry·Graham AtkinHenry L Paulson
Feb 6, 2015·Database : the Journal of Biological Databases and Curation·J M VillavecesHenning Hermjakob

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Citations

Jul 10, 2016·Journal of Biomedical Semantics·Anandhi IyappanPhilipp Senger
Jul 23, 2016·Briefings in Bioinformatics·Xiaoqing PengYi Pan
Jun 7, 2017·Expert Opinion on Drug Discovery·Marja TalikkaJulia Hoeng
Oct 23, 2018·Omics : a Journal of Integrative Biology·Avijit PodderLatha Narayanan
Mar 7, 2019·Current Topics in Medicinal Chemistry·Ankit GaneshpurkarSushil K Singh
Jul 28, 2020·Journal of Alzheimer's Disease : JAD·Lionel BreuzaUNKNOWN IMEx Consortium, UniProt Consortium

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Clinical Trials Mentioned

NCT01782742
NCT01584440

Software Mentioned

PSISCORE
InVitro
R script
Cytoscape
InVivo
MINT
SCAIView

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