Reference: Yu X, et al. (2009) A novel scoring approach for protein co-purification data reveals high interaction specificity. PLoS Comput Biol 5(9):e1000515

Reference Help

Abstract


Large-scale protein interaction networks (PINs) have typically been discerned using affinity purification followed by mass spectrometry (AP/MS) and yeast two-hybrid (Y2H) techniques. It is generally recognized that Y2H screens detect direct binary interactions while the AP/MS method captures co-complex associations; however, the latter technique is known to yield prevalent false positives arising from a number of effects, including abundance. We describe a novel approach to compute the propensity for two proteins to co-purify in an AP/MS data set, thereby allowing us to assess the detected level of interaction specificity by analyzing the corresponding distribution of interaction scores. We find that two recent AP/MS data sets of yeast contain enrichments of specific, or high-scoring, associations as compared to commensurate random profiles, and that curated, direct physical interactions in two prominent data bases have consistently high scores. Our scored interaction data sets are generally more comprehensive than those of previous studies when compared against four diverse, high-quality reference sets. Furthermore, we find that our scored data sets are more enriched with curated, direct physical associations than Y2H sets. A high-confidence protein interaction network (PIN) derived from the AP/MS data is revealed to be highly modular, and we show that this topology is not the result of misrepresenting indirect associations as direct interactions. In fact, we propose that the modularity in Y2H data sets may be underrepresented, as they contain indirect associations that are significantly enriched with false negatives. The AP/MS PIN is also found to contain significant assortative mixing; however, in line with a previous study we confirm that Y2H interaction data show weak disassortativeness, thus revealing more clearly the distinctive natures of the interaction detection methods. We expect that our scored yeast data sets are ideal for further biological discovery and that our scoring system will prove useful for other AP/MS data sets.

Reference Type
Journal Article | Research Support, U.S. Gov't, Non-P.H.S.
Authors
Yu X, Ivanic J, Wallqvist A, Reifman J
Primary Lit For
Additional Lit For
Review For

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Site Modification Modifier Reference

Interaction Annotations


Genetic Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Assay Annotation Action Modification Source Reference

Functional Complementation Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Species Gene ID Strain background Direction Details Source Reference