Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps
By Hailiang Huang, Bruno M. Jedynak, Joel S. Bader. 2007
154 citations recorded by the source corpus.
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.
Subfields: Cell Biology, Molecular Biology, Spectroscopy
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In Cell Biology
In Molecular Biology
- Anne-Ruxandra Carvunis
- S. Ramesh
- Koyel Mitra
- Trey Ideker
- Anastasia Baryshnikova
- Roded Sharan
- Donna K. Slonim
- Tommaso Cai
In Spectroscopy
Citations in the corpus
- Computed structures of core eukaryotic protein complexes (2021, unknown): “The ratio of confidently predicted PPIs is even lower for protein pairs identified by Y2H (18%) or APMS (14%) screens (table S1), consistent with the known larger fraction of false positives in large-scale experimental screens (8, 22).”
- Integrative approaches for finding modular structure in biological networks (2013, background): “Experimental artefacts, variability in coverage across data sets, sampling bias towards well-studied processes, limitations in screening power and inherent sensitivities in various assays can yield false positives and false negatives in interaction data 23–26 .”