Abstract:BackgroundOur knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods.ResultsOn the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network within 3 months. With a recall of 23% at a precision of 82.1%, we predicted 172,132 putative PPIs. We demonstrate the usefulness of these predictions through a range of experiments.ConclusionsThe spe… Show more
“…We have used the PIPE algorithm
[32–36] to predict interactomes for
all five species, and we provide a null model for PPI network evolution by
simulation. We find evidence for extensive conservation of PPIs, as might be
expected given the importance of PPIs for basic cellular functions.…”
Section: Discussionmentioning
confidence: 99%
“…These drawbacks include a reliance on unavailable or unreliable
biological data (evolutionary history, domains, 3D structure, etc. ), high
computational complexity leading to excessive run times, and unacceptably high
error rates, among others [36]. …”
Section: Methodsmentioning
confidence: 99%
“…To remain consistent across all predictions
made, this decision threshold was used across all strains, both real and
simulated. For more details on how these LOOCV tests are conducted see [36]. …”
Section: Methodsmentioning
confidence: 99%
“…Our computational inference makes use of the Protein-protein Interaction Prediction
Engine (PIPE), an algorithm that predicts PPIs on the basis of protein primary
sequence only [32–36]. PIPE breaks query proteins into short overlapping polypeptide segments and searches
within a list of known and experimentally verified PPIs to find similar segments.…”
Section: Introductionmentioning
confidence: 99%
“…Our ability to achieve such high specificity is a distinguishing
feature of PIPE [37], and is
critical when one intends to examine millions of protein pairs (effectively testing
millions of hypotheses). PIPE has been used to identify novel protein interactions,
to discover new protein complexes, to predict novel protein functions [32–36], and to produce
proteome-wide predicted interaction networks for S . cerevisiae [34], Schizosaccharomyces pombe [33], Caenorhabditis
elegans [35] and
Homo sapiens [36], among others.…”
Interest in the evolution of protein-protein and genetic interaction networks has
been rising in recent years, but the lack of large-scale high quality
comparative datasets has acted as a barrier. Here, we carried out a comparative
analysis of computationally predicted protein-protein interaction (PPI) networks
from five closely related yeast species. We used the Protein-protein Interaction
Prediction Engine (PIPE), which uses a database of known interactions to make
sequence-based PPI predictions, to generate high quality predicted interactomes.
Simulated proteomes and corresponding PPI networks were used to provide null
expectations for the extent and nature of PPI network evolution. We found strong
evidence for conservation of PPIs, with lower than expected levels of change in
PPIs for about a quarter of the proteome. Furthermore, we found that changes in
predicted PPI networks are poorly predicted by sequence divergence. Our analyses
identified a number of functional classes experiencing fewer PPI changes than
expected, suggestive of purifying selection on PPIs. Our results demonstrate the
added benefit of considering predicted PPI networks when studying the evolution
of closely related organisms.
“…We have used the PIPE algorithm
[32–36] to predict interactomes for
all five species, and we provide a null model for PPI network evolution by
simulation. We find evidence for extensive conservation of PPIs, as might be
expected given the importance of PPIs for basic cellular functions.…”
Section: Discussionmentioning
confidence: 99%
“…These drawbacks include a reliance on unavailable or unreliable
biological data (evolutionary history, domains, 3D structure, etc. ), high
computational complexity leading to excessive run times, and unacceptably high
error rates, among others [36]. …”
Section: Methodsmentioning
confidence: 99%
“…To remain consistent across all predictions
made, this decision threshold was used across all strains, both real and
simulated. For more details on how these LOOCV tests are conducted see [36]. …”
Section: Methodsmentioning
confidence: 99%
“…Our computational inference makes use of the Protein-protein Interaction Prediction
Engine (PIPE), an algorithm that predicts PPIs on the basis of protein primary
sequence only [32–36]. PIPE breaks query proteins into short overlapping polypeptide segments and searches
within a list of known and experimentally verified PPIs to find similar segments.…”
Section: Introductionmentioning
confidence: 99%
“…Our ability to achieve such high specificity is a distinguishing
feature of PIPE [37], and is
critical when one intends to examine millions of protein pairs (effectively testing
millions of hypotheses). PIPE has been used to identify novel protein interactions,
to discover new protein complexes, to predict novel protein functions [32–36], and to produce
proteome-wide predicted interaction networks for S . cerevisiae [34], Schizosaccharomyces pombe [33], Caenorhabditis
elegans [35] and
Homo sapiens [36], among others.…”
Interest in the evolution of protein-protein and genetic interaction networks has
been rising in recent years, but the lack of large-scale high quality
comparative datasets has acted as a barrier. Here, we carried out a comparative
analysis of computationally predicted protein-protein interaction (PPI) networks
from five closely related yeast species. We used the Protein-protein Interaction
Prediction Engine (PIPE), which uses a database of known interactions to make
sequence-based PPI predictions, to generate high quality predicted interactomes.
Simulated proteomes and corresponding PPI networks were used to provide null
expectations for the extent and nature of PPI network evolution. We found strong
evidence for conservation of PPIs, with lower than expected levels of change in
PPIs for about a quarter of the proteome. Furthermore, we found that changes in
predicted PPI networks are poorly predicted by sequence divergence. Our analyses
identified a number of functional classes experiencing fewer PPI changes than
expected, suggestive of purifying selection on PPIs. Our results demonstrate the
added benefit of considering predicted PPI networks when studying the evolution
of closely related organisms.
Protein molecules often interact with other partner protein molecules in order to execute their vital functions in living organisms. Characterization of protein-protein interactions thus plays a central role in understanding the molecular mechanism of relevant protein molecules, elucidating the cellular processes and pathways relevant to health or disease for drug discovery, and charting large-scale interaction networks in systems biology research. A whole spectrum of methods, based on biophysical, biochemical, or genetic principles, have been developed to detect the time, space, and functional relevance of protein-protein interactions at various degrees of affinity and specificity. This article presents an overview of these experimental methods, outlining the principles, strengths and limitations, and recent developments of each type of method.
E10 is a new maturity locus in soybean and FT4 is the predicted/potential functional gene underlying the locus. Flowering and maturity time traits play crucial roles in economic soybean production. Early maturity is critical for north and west expansion of soybean in Canada. To date, 11 genes/loci have been identified which control time to flowering and maturity; however, the molecular bases of almost half of them are not yet clear. We have identified a new maturity locus called "E10" located at the end of chromosome Gm08. The gene symbol E10e10 has been approved by the Soybean Genetics Committee. The e10e10 genotype results in 5-10 days earlier maturity than E10E10. A set of presumed E10E10 and e10e10 genotypes was used to identify contrasting SSR and SNP haplotypes. These haplotypes, and their association with maturity, were maintained through five backcross generations. A functional genomics approach using a predicted protein-protein interaction (PPI) approach (Protein-protein Interaction Prediction Engine, PIPE) was used to investigate approximately 75 genes located in the genomic region that SSR and SNP analyses identified as the location of the E10 locus. The PPI analysis identified FT4 as the most likely candidate gene underlying the E10 locus. Sequence analysis of the two FT4 alleles identified three SNPs, in the 5'UTR, 3'UTR and fourth exon in the coding region, which result in differential mRNA structures. Allele-specific markers were developed for this locus and are available for soybean breeders to efficiently develop earlier maturing cultivars using molecular marker assisted breeding.
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