Clustering with Overlap for Genetic Interaction Networks via Local Search Optimization

Algorithms for detection of modules in genetics interaction networks, while often identifying new models of functional modular organization between genes, have been limited to the output of disjoint, non-overlapping modules, while natural overlapping modules have been observed in biological networks. We present CLOVER, an algorithm for clustering weighted networks into overlapping clusters. We apply this algorithm to the correlation network obtained from a large-scale genetic interaction network of Saccharomyces cerevisiae derived from Synthetic Genetic Arrays (SGA) that covers ∼4,500 nonessential genes. We compare CLOVER to previous clustering methods, and demonstrate that genes assigned by our method to multiple clusters known to link distinct biological processes.

[1]  Katsuhiko Shirahige,et al.  Establishment of sister chromatid cohesion at the S. cerevisiae replication fork. , 2006, Molecular cell.

[2]  Charles Boone,et al.  Elg1 forms an alternative RFC complex important for DNA replication and genome integrity , 2003, The EMBO journal.

[3]  Gary D. Bader,et al.  An automated method for finding molecular complexes in large protein interaction networks , 2003, BMC Bioinformatics.

[4]  Michael C. Schatz,et al.  Revealing Biological Modules via Graph Summarization , 2009, J. Comput. Biol..

[5]  R. Fisher.  XV.—The Correlation between Relatives on the Supposition of Mendelian Inheritance. , 1919, Transactions of the Royal Society of Edinburgh.

[6]  Daphne Koller,et al.  A Complex-based Reconstruction of the Saccharomyces cerevisiae Interactome *S⃞ , 2009, Molecular & Cellular Proteomics.

[7]  Richard C. Jones,et al.  A key role for Ctf4 in coupling the MCM2‐7 helicase to DNA polymerase α within the eukaryotic replisome , 2009, The EMBO journal.

[8]  Igor Jurisica,et al.  Protein complex prediction via cost-based clustering , 2004, Bioinform..

[9]  Jacques van Helden,et al.  Evaluation of clustering algorithms for protein-protein interaction networks , 2006, BMC Bioinformatics.

[10]  Katsuhiko Shirahige,et al.  Csm3, Tof1, and Mrc1 Form a Heterotrimeric Mediator Complex That Associates with DNA Replication Forks , 2009, The Journal of Biological Chemistry.

[11]  Roded Sharan,et al.  Identification of protein complexes by comparative analysis of yeast and bacterial protein interaction data , 2004, J. Comput. Biol..

[12]  Gary D Bader,et al.  Global Mapping of the Yeast Genetic Interaction Network , 2004, Science.

[13]  R. Shamir,et al.  From E-MAPs to module maps: dissecting quantitative genetic interactions using physical interactions , 2008, Molecular Systems Biology.

[14]  Ron Shamir,et al.  A clustering algorithm based on graph connectivity , 2000, Inf. Process. Lett..

[15]  Brian D. Peyser,et al.  S-phase checkpoint genes safeguard high-fidelity sister chromatid cohesion. , 2004, Molecular biology of the cell.

[16]  G. Church,et al.  Modular epistasis in yeast metabolism , 2005, Nature Genetics.

[17]  Dmitry A. Gordenin,et al.  Flexibility of Eukaryotic Okazaki Fragment Maturation through Regulated Strand Displacement Synthesis* , 2008, Journal of Biological Chemistry.

[18]  Gary D Bader,et al.  The Genetic Landscape of a Cell , 2010, Science.

[19]  T. Ideker,et al.  Systematic interpretation of genetic interactions using protein networks , 2005, Nature Biotechnology.

[20]  Daniel Durocher,et al.  Elg1 Forms an Alternative PCNA-Interacting RFC Complex Required to Maintain Genome Stability , 2003, Current Biology.

[21]  S. Gygi,et al.  Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae. , 2001, Molecular cell.

[22]  Hiroyuki Araki,et al.  Ctf4 coordinates the progression of helicase and DNA polymerase α , 2009, Genes to cells : devoted to molecular & cellular mechanisms.

[23]  R. Shamir,et al.  Pathway redundancy and protein essentiality revealed in the Saccharomyces cerevisiae interaction networks , 2007, Molecular systems biology.

[24]  J Majka,et al.  Structure of DNA Polymerase δ from Saccharomyces cerevisiae * , 2001, The Journal of Biological Chemistry.

[25]  O. Aparicio,et al.  Mrc1 is required for normal progression of replication forks throughout chromatin in S. cerevisiae. , 2005, Molecular cell.

[26]  R. Bambara,et al.  Flap endonuclease 1: a central component of DNA metabolism. , 2004, Annual review of biochemistry.

[27]  S. Dongen.  A cluster algorithm for graphs , 2000 .

[28]  Ricky D. Edmondson,et al.  GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks , 2006, Nature Cell Biology.

[29]  Dmitrij Frishman,et al.  MIPS: a database for genomes and protein sequences , 2000, Nucleic Acids Res..

[30]  F. Spencer,et al.  Saccharomyces cerevisiae CTF18 and CTF4 Are Required for Sister Chromatid Cohesion , 2001, Molecular and Cellular Biology.

[31]  Grant W. Brown,et al.  Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map , 2007, Nature.

[32]  Sean R. Collins,et al.  Exploration of the Function and Organization of the Yeast Early Secretory Pathway through an Epistatic Miniarray Profile , 2005, Cell.

[33]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[34]  Martin Kupiec,et al.  ELG1, a yeast gene required for genome stability, forms a complex related to replication factor C , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  T. Vicsek,et al.  Uncovering the overlapping community structure of complex networks in nature and society , 2005, Nature.