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A semi-quantitative, synteny-based method to improve functional predictions for hypothetical and poorly annotated bacterial and archaeal genes.

ABSTRACT: During microbial evolution, genome rearrangement increases with increasing sequence divergence. If the relationship between synteny and sequence divergence can be modeled, gene clusters in genomes of distantly related organisms exhibiting anomalous synteny can be identified and used to infer functional conservation. We applied the phylogenetic pairwise comparison method to establish and model a strong correlation between synteny and sequence divergence in all 634 available Archaeal and Bacterial genomes from the NCBI database and four newly assembled genomes of uncultivated Archaea from an acid mine drainage (AMD) community. In parallel, we established and modeled the trend between synteny and functional relatedness in the 118 genomes available in the STRING database. By combining these models, we developed a gene functional annotation method that weights evolutionary distance to estimate the probability of functional associations of syntenous proteins between genome pairs. The method was applied to the hypothetical proteins and poorly annotated genes in newly assembled acid mine drainage Archaeal genomes to add or improve gene annotations. This is the first method to assign possible functions to poorly annotated genes through quantification of the probability of gene functional relationships based on synteny at a significant evolutionary distance, and has the potential for broad application.

SUBMITTER: Yelton AP

PROVIDER: S-EPMC3197636 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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A semi-quantitative, synteny-based method to improve functional predictions for hypothetical and poorly annotated bacterial and archaeal genes.

Yelton Alexis P AP Thomas Brian C BC Simmons Sheri L SL Wilmes Paul P Zemla Adam A Thelen Michael P MP Justice Nicholas N Banfield Jillian F JF

PLoS computational biology 20111020 10

During microbial evolution, genome rearrangement increases with increasing sequence divergence. If the relationship between synteny and sequence divergence can be modeled, gene clusters in genomes of distantly related organisms exhibiting anomalous synteny can be identified and used to infer functional conservation. We applied the phylogenetic pairwise comparison method to establish and model a strong correlation between synteny and sequence divergence in all 634 available Archaeal and Bacterial ...[more]

PMID: 22028637

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Project description:BackgroundThe methods with which prediction models are usually developed mean that neither the parameters nor the predictions should be interpreted causally. For many applications, this is perfectly acceptable. However, when prediction models are used to support decision making, there is often a need for predicting outcomes under hypothetical interventions.AimsWe aimed to identify published methods for developing and validating prediction models that enable risk estimation of outcomes under hypothetical interventions, utilizing causal inference. We aimed to identify the main methodological approaches, their underlying assumptions, targeted estimands, and potential pitfalls and challenges with using the method. Finally, we aimed to highlight unresolved methodological challenges.MethodsWe systematically reviewed literature published by December 2019, considering papers in the health domain that used causal considerations to enable prediction models to be used for predictions under hypothetical interventions. We included both methodologies proposed in statistical/machine learning literature and methodologies used in applied studies.ResultsWe identified 4919 papers through database searches and a further 115 papers through manual searches. Of these, 87 papers were retained for full-text screening, of which 13 were selected for inclusion. We found papers from both the statistical and the machine learning literature. Most of the identified methods for causal inference from observational data were based on marginal structural models and g-estimation.ConclusionsThere exist two broad methodological approaches for allowing prediction under hypothetical intervention into clinical prediction models: (1) enriching prediction models derived from observational studies with estimated causal effects from clinical trials and meta-analyses and (2) estimating prediction models and causal effects directly from observational data. These methods require extending to dynamic treatment regimes, and consideration of multiple interventions to operationalise a clinical decision support system. Techniques for validating 'causal prediction models' are still in their infancy.

Project description:BackgroundCross-validation tools are used increasingly to validate and compare genetic evaluation methods but analytical properties of cross-validation methods are rarely described. There is also a lack of cross-validation tools for complex problems such as prediction of indirect effects (e.g. maternal effects) or for breeding schemes with small progeny group sizes.ResultsWe derive the expected value of several quadratic forms by comparing genetic evaluations including "partial" and "whole" data. We propose statistics that compare genetic evaluations including "partial" and "whole" data based on differences in means, covariance, and correlation, and term the use of these statistics "method LR" (from linear regression). Contrary to common belief, the regression of true on estimated breeding values is (on expectation) lower than 1 for small or related validation sets, due to family structures. For validation sets that are sufficiently large, we show that these statistics yield estimators of bias, slope or dispersion, and population accuracy for estimated breeding values. Similar results hold for prediction of future phenotypes although we show that estimates of bias, slope or dispersion using prediction of future phenotypes are sensitive to incorrect heritabilities or precorrection for fixed effects. We present an example for a set of 2111 Brahman beef cattle for which, in repeated partitioning of the data into training and validation sets, there is very good agreement of statistics of method LR with prediction of future phenotypes.ConclusionsAnalytical properties of cross-validation measures are presented. We present a new method named LR for cross-validation that is automatic, easy to use, and which yields the quantities of interest. The method compares predictions based on partial and whole data, which results in estimates of accuracy and biases. Prediction of observed records may yield biased results due to precorrection or use of incorrect heritabilities.

Dataset Information

A semi-quantitative, synteny-based method to improve functional predictions for hypothetical and poorly annotated bacterial and archaeal genes.

Publications

A semi-quantitative, synteny-based method to improve functional predictions for hypothetical and poorly annotated bacterial and archaeal genes.

Similar Datasets

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