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Towards accurate imputation of quantitative genetic interactions.

Ulitsky I, Krogan NJ, Shamir R - Genome Biol. (2009)

Bottom Line: Recent technological breakthroughs have enabled high-throughput quantitative measurements of hundreds of thousands of genetic interactions among hundreds of genes in Saccharomyces cerevisiae.Here we present a novel method, which combines genetic interaction data together with diverse genomic data, to quantitatively impute these missing interactions.We also present data on almost 190,000 novel interactions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel. ulitsky@wi.mit.edu

ABSTRACT
Recent technological breakthroughs have enabled high-throughput quantitative measurements of hundreds of thousands of genetic interactions among hundreds of genes in Saccharomyces cerevisiae. However, these assays often fail to measure the genetic interactions among up to 40% of the studied gene pairs. Here we present a novel method, which combines genetic interaction data together with diverse genomic data, to quantitatively impute these missing interactions. We also present data on almost 190,000 novel interactions.

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Genetic interactions within protein complexes. (a, b) Percent of gene pairs within complexes that have a negative GI between them. (a) Complexes with at least 20% negative interactions. (b) Complexes with at least 20% positive interactions. (c, d) Examples of representative protein complexes enriched with negative (c) or positive (d) GIs. For each complex the matrix presents the combined measured and predicted data. Measured GIs are marked by a yellow dot. No GIs were measured in the complexes in (c). Essential gene names are in red.
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Figure 8: Genetic interactions within protein complexes. (a, b) Percent of gene pairs within complexes that have a negative GI between them. (a) Complexes with at least 20% negative interactions. (b) Complexes with at least 20% positive interactions. (c, d) Examples of representative protein complexes enriched with negative (c) or positive (d) GIs. For each complex the matrix presents the combined measured and predicted data. Measured GIs are marked by a yellow dot. No GIs were measured in the complexes in (c). Essential gene names are in red.

Mentions: We selected all the complexes described in a recent yeast protein complex curation [33] that contained at least three genes in the ChromBio set. Of these complexes, 38 contained at least one positive or negative GI after imputation using linear regression and all the features; and 17 (15) were significantly enriched with positive (negative) GIs (false discovery rate < 0.05; see Materials and methods; Figure 8a, b). Bandyopadhyay et al. [17] identified 19 modules (corresponding to putative complexes or pathways) that were enriched for positive interactions and 9 enriched for negative ones. In contrast, we found that the number of complexes enriched with negative interactions is comparable to that of complexes enriched with positive interactions. This is probably because we were able to analyze additional complexes that are enriched with negative interactions (see below).


Towards accurate imputation of quantitative genetic interactions.

Ulitsky I, Krogan NJ, Shamir R - Genome Biol. (2009)

Genetic interactions within protein complexes. (a, b) Percent of gene pairs within complexes that have a negative GI between them. (a) Complexes with at least 20% negative interactions. (b) Complexes with at least 20% positive interactions. (c, d) Examples of representative protein complexes enriched with negative (c) or positive (d) GIs. For each complex the matrix presents the combined measured and predicted data. Measured GIs are marked by a yellow dot. No GIs were measured in the complexes in (c). Essential gene names are in red.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2812947&req=5

Figure 8: Genetic interactions within protein complexes. (a, b) Percent of gene pairs within complexes that have a negative GI between them. (a) Complexes with at least 20% negative interactions. (b) Complexes with at least 20% positive interactions. (c, d) Examples of representative protein complexes enriched with negative (c) or positive (d) GIs. For each complex the matrix presents the combined measured and predicted data. Measured GIs are marked by a yellow dot. No GIs were measured in the complexes in (c). Essential gene names are in red.
Mentions: We selected all the complexes described in a recent yeast protein complex curation [33] that contained at least three genes in the ChromBio set. Of these complexes, 38 contained at least one positive or negative GI after imputation using linear regression and all the features; and 17 (15) were significantly enriched with positive (negative) GIs (false discovery rate < 0.05; see Materials and methods; Figure 8a, b). Bandyopadhyay et al. [17] identified 19 modules (corresponding to putative complexes or pathways) that were enriched for positive interactions and 9 enriched for negative ones. In contrast, we found that the number of complexes enriched with negative interactions is comparable to that of complexes enriched with positive interactions. This is probably because we were able to analyze additional complexes that are enriched with negative interactions (see below).

Bottom Line: Recent technological breakthroughs have enabled high-throughput quantitative measurements of hundreds of thousands of genetic interactions among hundreds of genes in Saccharomyces cerevisiae.Here we present a novel method, which combines genetic interaction data together with diverse genomic data, to quantitatively impute these missing interactions.We also present data on almost 190,000 novel interactions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel. ulitsky@wi.mit.edu

ABSTRACT
Recent technological breakthroughs have enabled high-throughput quantitative measurements of hundreds of thousands of genetic interactions among hundreds of genes in Saccharomyces cerevisiae. However, these assays often fail to measure the genetic interactions among up to 40% of the studied gene pairs. Here we present a novel method, which combines genetic interaction data together with diverse genomic data, to quantitatively impute these missing interactions. We also present data on almost 190,000 novel interactions.

Show MeSH
Related in: MedlinePlus