Cargando…
Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps
Yeast two-hybrid screens are an important method for mapping pairwise physical interactions between proteins. The fraction of interactions detected in independent screens can be very small, and an outstanding challenge is to determine the reason for the low overlap. Low overlap can arise from either...
Autores principales: | , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2007
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082503/ https://www.ncbi.nlm.nih.gov/pubmed/18039026 http://dx.doi.org/10.1371/journal.pcbi.0030214 |
_version_ | 1782138175098978304 |
---|---|
author | Huang, Hailiang Jedynak, Bruno M Bader, Joel S |
author_facet | Huang, Hailiang Jedynak, Bruno M Bader, Joel S |
author_sort | Huang, Hailiang |
collection | PubMed |
description | Yeast two-hybrid screens are an important method for mapping pairwise physical interactions between proteins. The fraction of interactions detected in independent screens can be very small, and an outstanding challenge is to determine the reason for the low overlap. Low overlap can arise from either a high false-discovery rate (interaction sets have low overlap because each set is contaminated by a large number of stochastic false-positive interactions) or a high false-negative rate (interaction sets have low overlap because each misses many true interactions). We extend capture–recapture theory to provide the first unified model for false-positive and false-negative rates for two-hybrid screens. Analysis of yeast, worm, and fly data indicates that 25% to 45% of the reported interactions are likely false positives. Membrane proteins have higher false-discovery rates on average, and signal transduction proteins have lower rates. The overall false-negative rate ranges from 75% for worm to 90% for fly, which arises from a roughly 50% false-negative rate due to statistical undersampling and a 55% to 85% false-negative rate due to proteins that appear to be systematically lost from the assays. Finally, statistical model selection conclusively rejects the Erdös-Rényi network model in favor of the power law model for yeast and the truncated power law for worm and fly degree distributions. Much as genome sequencing coverage estimates were essential for planning the human genome sequencing project, the coverage estimates developed here will be valuable for guiding future proteomic screens. All software and datasets are available in Datasets S1 and S2, Figures S1–S5, and Tables S1−S6, and are also available from our Web site, http://www.baderzone.org. |
format | Text |
id | pubmed-2082503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-20825032007-11-29 Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps Huang, Hailiang Jedynak, Bruno M Bader, Joel S PLoS Comput Biol Research Article Yeast two-hybrid screens are an important method for mapping pairwise physical interactions between proteins. The fraction of interactions detected in independent screens can be very small, and an outstanding challenge is to determine the reason for the low overlap. Low overlap can arise from either a high false-discovery rate (interaction sets have low overlap because each set is contaminated by a large number of stochastic false-positive interactions) or a high false-negative rate (interaction sets have low overlap because each misses many true interactions). We extend capture–recapture theory to provide the first unified model for false-positive and false-negative rates for two-hybrid screens. Analysis of yeast, worm, and fly data indicates that 25% to 45% of the reported interactions are likely false positives. Membrane proteins have higher false-discovery rates on average, and signal transduction proteins have lower rates. The overall false-negative rate ranges from 75% for worm to 90% for fly, which arises from a roughly 50% false-negative rate due to statistical undersampling and a 55% to 85% false-negative rate due to proteins that appear to be systematically lost from the assays. Finally, statistical model selection conclusively rejects the Erdös-Rényi network model in favor of the power law model for yeast and the truncated power law for worm and fly degree distributions. Much as genome sequencing coverage estimates were essential for planning the human genome sequencing project, the coverage estimates developed here will be valuable for guiding future proteomic screens. All software and datasets are available in Datasets S1 and S2, Figures S1–S5, and Tables S1−S6, and are also available from our Web site, http://www.baderzone.org. Public Library of Science 2007-11 2007-11-23 /pmc/articles/PMC2082503/ /pubmed/18039026 http://dx.doi.org/10.1371/journal.pcbi.0030214 Text en © 2007 Huang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Huang, Hailiang Jedynak, Bruno M Bader, Joel S Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps |
title | Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps |
title_full | Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps |
title_fullStr | Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps |
title_full_unstemmed | Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps |
title_short | Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps |
title_sort | where have all the interactions gone? estimating the coverage of two-hybrid protein interaction maps |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082503/ https://www.ncbi.nlm.nih.gov/pubmed/18039026 http://dx.doi.org/10.1371/journal.pcbi.0030214 |
work_keys_str_mv | AT huanghailiang wherehavealltheinteractionsgoneestimatingthecoverageoftwohybridproteininteractionmaps AT jedynakbrunom wherehavealltheinteractionsgoneestimatingthecoverageoftwohybridproteininteractionmaps AT baderjoels wherehavealltheinteractionsgoneestimatingthecoverageoftwohybridproteininteractionmaps |