title: A survey of protein interaction data and multigenic inherited disorders.
abstract: BACKGROUND
  Multigenic diseases are often associated with protein complexes or interactions involved in the same pathway. We wanted to estimate to what extent this is true given a consolidated protein interaction data set. The study stresses data integration and data representation issues.
  
  
  RESULTS
  We constructed 497 multigenic disease groups from OMIM and tested for overlaps with interaction and pathway data. A total of 159 disease groups had significant overlaps with protein interaction data consolidated by iRefIndex. A further 68 disease overlaps were found only in the KEGG pathway database. No single database contained all significant overlaps thus stressing the importance of data integration. We also found that disease groups overlapped with all three interaction data types: n-ary, spoke-represented complexes and binary data - thus stressing the importance of considering each of these data types separately.
  
  
  CONCLUSIONS
  Almost half of our multigenic disease groups could potentially be explained by protein complexes and pathways. However, the fact that no database or data type was able to cover all disease groups suggests that no single database has systematically covered all disease groups for potential related complex and pathway data. This survey provides a basis for further curation efforts to confirm and search for overlaps between diseases and interaction data. The accompanying R script can be used to reproduce the work and track progress in this area as databases change. Disease group overlaps can be further explored using the iRefscape plugin for Cytoscape.
authors: Department for Molecular Biosciences, University of Oslo, P.O. Box 1041 Blindern, 0316, Oslo, Norway.
authors: Antonio
authors: A
authors: Mora
authors: Katerina
authors: K
authors: Michalickova
authors: Ian M
authors: IM
authors: Donaldson
mesh_terms: D000465:Algorithms; D030541:Databases, Genetic; D030562:Databases, Protein; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D020158:Hyperglycinemia, Nonketotic / Q000235:genetics; D056929:Liddle Syndrome / Q000235:genetics; D046912:Multiprotein Complexes / Q000235:genetics*; D009394:Nephritis, Hereditary / Q000235:genetics; D025941:Protein Interaction Mapping
chemical_list: D046912:Multiprotein Complexes
references: Am J Hum Genet. 2007 Apr;80(4):588-604
references: 17357067
references: Biochemistry (Mosc). 2011 Jan;76(1):36-48
references: 21568838
references: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4372-6
references: 12676999
references: BMC Bioinformatics. 2011 Nov 24;12:455
references: 22115179
references: BMC Bioinformatics. 2011 Oct 05;12:388
references: 21975162
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D767-72
references: 18988627
references: J Am Soc Nephrol. 2004 Oct;15(10):2514-27
references: 15466256
references: Database (Oxford). 2010 Oct 12;2010:baq023
references: 20940177
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D532-9
references: 19897547
references: Nat Biotechnol. 2007 Mar;25(3):309-16
references: 17344885
references: Nucleic Acids Res. 2009 Jan;37(1):1-13
references: 19033363
references: Bioinformatics. 2005 Mar;21(6):832-4
references: 15531608
references: Am J Physiol Renal Physiol. 2004 Jun;286(6):F1100-6
references: 14996668
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D698-704
references: 21071413
references: Bioinformatics. 2005 May 1;21(9):2076-82
references: 15657099
references: Brief Bioinform. 2007 Sep;8(5):333-46
references: 17638813
references: Proc Natl Acad Sci U S A. 2007 May 22;104(21):8685-90
references: 17502601
references: Database (Oxford). 2010 Dec 22;2010:baq026
references: 21183497
references: Nat Protoc. 2009;4(1):44-57
references: 19131956
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D525-31
references: 19850723
references: BMC Bioinformatics. 2008 Sep 30;9:405
references: 18823568
references: Nat Genet. 2004 May;36(5):431-2
references: 15118671
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D235-40
references: 20852260
references: BMC Med Inform Decis Mak. 2008 Oct 27;8 Suppl 1:S2
references: 19007439
references: Nucleic Acids Res. 2002 Jan 1;30(1):303-5
references: 11752321
references: Mol Syst Biol. 2008;4:218
references: 18766178
references: Nat Rev Genet. 2002 Oct;3(10):779-89
references: 12360236
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D646-50
references: 17965090
references: Bioinformatics. 2009 Mar 15;25(6):830-1
references: 19176557
references: Clin Genet. 2007 Jan;71(1):1-11
references: 17204041
references: Nucleic Acids Res. 2000 Jan 1;28(1):27-30
references: 10592173
references: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4323-8
references: 18326631
references: Nucleic Acids Res. 2001 Jan 1;29(1):242-5
references: 11125103
references: Nat Methods. 2012 Apr;9(4):345-50
references: 22453911