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Computational Prediction of Protein–Protein Interaction Networks: Algorithms and Resources Keywords: protein-protein interactions Databases Database sizes Gene duplication Neofunctionalization Subfunctionalization Nicola Pezzotti Maryam Soleimani Dodaran Saman Amini Protein-Protein-Interactions • Lasting and specific physical contact established by two or more proteins – Biochemical events – Electrostatic forces • Molecular processes are built from a large protein compound organized by PPIs Databases (PPI) • > 100 databases • Redundant data – Efforts for integration • HUPO-PSI • IMEx (www.imexconsortium.org) Popular repositories (I) • BioGRID (IMEx) – Experimentally determined protein-protein interactions – 27 organisms – 460000 interactions • DIP (IMEx) – 460 organisms • BIND (IMEx) – 200000 interactions – 1500 organisms – Contains interactions involving RNA, DNA, genes, complexes and small molecules – Curation stopped in 2005 (!) Popular repositories (II) • MINT (IMEx) – 230000 interactions – 34000 proteins – Contains confidence scores • HPRD – – – – Human proteins interactions Manually extracted from literature 30000 proteins 39000 PPIs • IntAct (IMEx) – – – – Molecular interaction DB 60000 proteins 290000 binary interactions Extracted from 5000 scientific publications Gene duplication • Refers to the duplication of a segment of DNA that contains one or more genes. • Gene duplication is the primary source of new genes in evolution, and duplicate genes form gene families that are abundantly found in almost all genomes Some gene duplicates may still be functionally redundant Gene duplication • Refers to the duplication of a segment of DNA that contains one or more genes. • Gene duplication is the primary source of new genes in evolution, and duplicate genes form gene families that are abundantly found in almost all genomes Some gene duplicates may still be functionally redundant Van Wageningen et al, 2010 Gene duplication • Whole genome duplication (WGD) • Small Scale duplication (SSD) Kellis et al., 2004 Hypothetical example of network evolution following a genome duplication Two reasons for the loss and gain of new interactions: • Neofunctionalization • Subfunctionalization Conant and Wolfe, 2008 Neofunctionalization: one of the two genes possesses a new, selectively beneficial function that was absent in the population before the duplication. Subfunctionalization: The functions of an ancestrally multifunctional gene have become divided up neutrally among the daughter copies.
