Dataset Information

Toward Reducing Phylostratigraphic Errors and Biases.

ABSTRACT: Phylostratigraphy is a method for estimating gene age, usually applied to large numbers of genes in order to detect nonrandom age-distributions of gene properties that could shed light on mechanisms of gene origination and evolution. However, phylostratigraphy underestimates gene age with a nonnegligible probability. The underestimation is severer for genes with certain properties, creating spurious age distributions of these properties and those correlated with these properties. Here we explore three strategies to reduce phylostratigraphic error/bias. First, we test several alternative homology detection methods (PSIBLAST, HMMER, PHMMER, OMA, and GLAM2Scan) in phylostratigraphy, but fail to find any that noticeably outperforms the commonly used BLASTP. Second, using machine learning, we look for predictors of error-prone genes to exclude from phylostratigraphy, but cannot identify reliable predictors. Finally, we remove from phylostratigraphic analysis genes exhibiting errors in simulation, which by definition minimizes error/bias if the simulation is sufficiently realistic. Using this last approach, we show that some previously reported phylostratigraphic trends (e.g., younger proteins tend to evolve more rapidly and be shorter) disappear or even reverse, reconfirming the necessity of controlling phylostratigraphic error/bias. Taken together, our analyses demonstrate that phylostratigraphic errors/biases are refractory to several potential solutions but can be controlled at least partially by the exclusion of error-prone genes identified via realistic simulations. These results are expected to stimulate the judicious use of error-aware phylostratigraphy and reevaluation of previous phylostratigraphic findings.

SUBMITTER: Moyers BA

PROVIDER: S-EPMC6105108 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Toward Reducing Phylostratigraphic Errors and Biases.

Moyers Bryan A BA Zhang Jianzhi J

Genome biology and evolution 20180801 8

Phylostratigraphy is a method for estimating gene age, usually applied to large numbers of genes in order to detect nonrandom age-distributions of gene properties that could shed light on mechanisms of gene origination and evolution. However, phylostratigraphy underestimates gene age with a nonnegligible probability. The underestimation is severer for genes with certain properties, creating spurious age distributions of these properties and those correlated with these properties. Here we explore ...[more]

PMID: 30060201

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Project description:In real life, we often have to make judgements under uncertainty. One such judgement task is estimating the probability of a given event based on uncertain evidence for the event, such as estimating the chances of actual fire when the fire alarm goes off. On the one hand, previous studies have shown that human subjects often significantly misestimate the probability in such cases. On the other hand, these studies have offered divergent explanations as to the exact causes of these judgment errors (or, synonymously, biases). For instance, different studies have attributed the errors to the neglect (or underweighting) of the prevalence (or base rate) of the given event, or the overweighting of the evidence for the individual event (‘individuating information’), etc. However, whether or to what extent any such explanation can fully account for the observed errors remains unclear. To help fill this gap, we studied the probability estimation performance of non-professional subjects under four different real-world problem scenarios: (i) Estimating the probability of cancer in a mammogram given the relevant evidence from a computer-aided cancer detection system, (ii) estimating the probability of drunkenness based on breathalyzer evidence, and (iii & iv) estimating the probability of an enemy sniper based on two different sets of evidence from a drone reconnaissance system. In each case, we quantitatively characterized the contributions of the various potential explanatory variables to the subjects’ probability judgements. We found that while the various explanatory variables together accounted for about 30 to 45% of the overall variance of the subjects’ responses depending on the problem scenario, no single factor was sufficient to account for more than 53% of the explainable variance (or about 16 to 24% of the overall variance), let alone all of it. Further analyses of the explained variance revealed the surprising fact that no single factor accounted for significantly more than its ‘fair share’ of the variance. Taken together, our results demonstrate quantitatively that it is statistically untenable to attribute the errors of probabilistic judgement to any single cause, including base rate neglect. A more nuanced and unifying explanation would be that the actual biases reflect a weighted combination of multiple contributing factors, the exact mix of which depends on the particular problem scenario.

Dataset Information

Toward Reducing Phylostratigraphic Errors and Biases.

Publications

Toward Reducing Phylostratigraphic Errors and Biases.

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