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Correcting for the study bias associated with protein-protein interaction measurements reveals differences between protein degree distributions from different cancer types.

ABSTRACT: Protein-protein interaction (PPI) networks are associated with multiple types of biases partly rooted in technical limitations of the experimental techniques. Another source of bias are the different frequencies with which proteins have been studied for interaction partners. It is generally believed that proteins with a large number of interaction partners tend to be essential, evolutionarily conserved, and involved in disease. It has been repeatedly reported that proteins driving tumor formation have a higher number of PPI partners. However, it has been noticed before that the degree distribution of PPI networks is biased toward disease proteins, which tend to have been studied more often than non-disease proteins. At the same time, for many poorly characterized proteins no interactions have been reported yet. It is unclear to which extent this study bias affects the observation that cancer proteins tend to have more PPI partners. Here, we show that the degree of a protein is a function of the number of times it has been screened for interaction partners. We present a randomization-based method that controls for this bias to decide whether a group of proteins is associated with significantly more PPI partners than the proteomic background. We apply our method to cancer proteins and observe, in contrast to previous studies, no conclusive evidence for a significantly higher degree distribution associated with cancer proteins as compared to non-cancer proteins when we compare them to proteins that have been equally often studied as bait proteins. Comparing proteins from different tumor types, a more complex picture emerges in which proteins of certain cancer classes have significantly more interaction partners while others are associated with a smaller degree. For example, proteins of several hematological cancers tend to be associated with a higher number of interaction partners as expected by chance. Solid tumors, in contrast, are usually associated with a degree distribution similar to those of equally often studied random protein sets. We discuss the biological implications of these findings. Our work shows that accounting for biases in the PPI network is possible and increases the value of PPI data.

SUBMITTER: Schaefer MH

PROVIDER: S-EPMC4523822 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Correcting for the study bias associated with protein-protein interaction measurements reveals differences between protein degree distributions from different cancer types.

Schaefer Martin H MH Serrano Luis L Andrade-Navarro Miguel A MA

Frontiers in genetics 20150804

Protein-protein interaction (PPI) networks are associated with multiple types of biases partly rooted in technical limitations of the experimental techniques. Another source of bias are the different frequencies with which proteins have been studied for interaction partners. It is generally believed that proteins with a large number of interaction partners tend to be essential, evolutionarily conserved, and involved in disease. It has been repeatedly reported that proteins driving tumor formatio ...[more]

PMID: 26300911

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Project description:A species sensitivity distribution (SSD) is a cumulative distribution function of toxicity endpoints for a receptor group. A key assumption when deriving an SSD is that the toxicity data points are independent and identically distributed (iid). This assumption is tenuous, however, because closely related species are more likely to have similar sensitivities than are distantly related species. When the response of 1 species can be partially predicted by the response of another species, there is a dependency or autocorrelation in the data set. To date, phylogenetic relationships and the resulting dependencies in input data sets have been ignored in deriving SSDs. In this paper, we explore the importance of the phylogenetic signal in deriving SSDs using a case studies approach. The case studies involved toxicity data sets for aquatic autotrophs exposed to atrazine and aquatic and avian species exposed to chlorpyrifos. Full and partial data sets were included to explore the influences of differing phylogenetic signal strength and sample size. The phylogenetic signal was significant for some toxicity data sets (i.e., most chlorpyrifos data sets) but not for others (i.e., the atrazine data sets, the chlorpyrifos data sets for all insects, crustaceans, and birds). When a significant phylogenetic signal did occur, effective sample size was reduced. The reduction was large when the signal was strong. In spite of the reduced effective sample sizes, significant phylogenetic signals had little impact on fitted SSDs, even in the tails (e.g., hazardous concentration for 5th percentile species [HC5]). The lack of a phylogenetic signal impact occurred even when we artificially reduced original sample size and increased strength of the phylogenetic signal. We conclude that it is good statistical practice to account for the phylogenetic signal when deriving SSDs because most toxicity data sets do not meet the independence assumption. That said, SSDs and HC5s are robust to deviations from the independence assumption. Integr Environ Assess Manag 2019;00:1-13. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Dataset Information

Correcting for the study bias associated with protein-protein interaction measurements reveals differences between protein degree distributions from different cancer types.

Publications

Correcting for the study bias associated with protein-protein interaction measurements reveals differences between protein degree distributions from different cancer types.

Similar Datasets

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