An integrated computational proteomics method to extract protein targets for fanconi anemia studies

Jake Yue Chen, Sarah L. Pinkerton, Changyu Shen, Mu Wang

Research output: Chapter in Book/Report/Conference proceedingConference contribution

6 Scopus citations

Abstract

Fanconi Anemia (FA) is a rare autosomal genetic disease with multiple birth defects and severe childhood complications for its patients. The lack of sequence homology of the entire FA Complementation Group proteins in such as FANCC, FANCG, FANCA makes them extremely difficult to characterize using conventional bioinformatics methods. In this work, we describe how to use computational methods to extract protein targets for FA, using protein interaction data set collected for FANC group C protein (FANCC). We first generated an initial set of 130 FA-interacting proteins as "FANCC seed proteins" by merging an in-house experimental set of FANCC Tandem Affinity Purification (TAP) Pulldown Proteomics data identified from Mass Spectrometry methods with publicly available human FANCC-interacting proteins. Next, we expanded the FANCC seed proteins using a nearest-neighbor method to generate a FANCC protein interaction subnetwork of 948 proteins in 903 protein interactions. We show that this network is statistically significant, with high indices of aggregation and separations. We also show a visualization of the network, support the evidence that many well-connected proteins exists in the network. Further, we developed and applied an interaction network protein scoring algorithm, which allows us to calculate a ranked list of significant FA proteins. Our result has been supporting further biological investigations of disease biologists on our team. We believe our method can be generalized to other disease biology studies with similar problems.

Original languageEnglish (US)
Title of host publicationApplied Computing 2006 - The 21st Annual ACM Symposium on Applied Computing - Proceedings of the 2006 ACM Symposium on Applied Computing
Pages173-179
Number of pages7
StatePublished - Nov 21 2006
Event2006 ACM Symposium on Applied Computing - Dijon, France
Duration: Apr 23 2006Apr 27 2006

Publication series

NameProceedings of the ACM Symposium on Applied Computing
Volume1

Other

Other2006 ACM Symposium on Applied Computing
CountryFrance
CityDijon
Period4/23/064/27/06

Keywords

  • Disease target
  • Fanconi anemia
  • Protein interaction network
  • Proteomics

ASJC Scopus subject areas

  • Computer Science(all)

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    Chen, J. Y., Pinkerton, S. L., Shen, C., & Wang, M. (2006). An integrated computational proteomics method to extract protein targets for fanconi anemia studies. In Applied Computing 2006 - The 21st Annual ACM Symposium on Applied Computing - Proceedings of the 2006 ACM Symposium on Applied Computing (pp. 173-179). (Proceedings of the ACM Symposium on Applied Computing; Vol. 1).