Dataset Information

Systematic planning of genome-scale experiments in poorly studied species.

ABSTRACT: Genome-scale datasets have been used extensively in model organisms to screen for specific candidates or to predict functions for uncharacterized genes. However, despite the availability of extensive knowledge in model organisms, the planning of genome-scale experiments in poorly studied species is still based on the intuition of experts or heuristic trials. We propose that computational and systematic approaches can be applied to drive the experiment planning process in poorly studied species based on available data and knowledge in closely related model organisms. In this paper, we suggest a computational strategy for recommending genome-scale experiments based on their capability to interrogate diverse biological processes to enable protein function assignment. To this end, we use the data-rich functional genomics compendium of the model organism to quantify the accuracy of each dataset in predicting each specific biological process and the overlap in such coverage between different datasets. Our approach uses an optimized combination of these quantifications to recommend an ordered list of experiments for accurately annotating most proteins in the poorly studied related organisms to most biological processes, as well as a set of experiments that target each specific biological process. The effectiveness of this experiment- planning system is demonstrated for two related yeast species: the model organism Saccharomyces cerevisiae and the comparatively poorly studied Saccharomyces bayanus. Our system recommended a set of S. bayanus experiments based on an S. cerevisiae microarray data compendium. In silico evaluations estimate that less than 10% of the experiments could achieve similar functional coverage to the whole microarray compendium. This estimation was confirmed by performing the recommended experiments in S. bayanus, therefore significantly reducing the labor devoted to characterize the poorly studied genome. This experiment-planning framework could readily be adapted to the design of other types of large-scale experiments as well as other groups of organisms.

SUBMITTER: Guan Y

PROVIDER: S-EPMC2832676 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Systematic planning of genome-scale experiments in poorly studied species.

Guan Yuanfang Y Dunham Maitreya M Caudy Amy A Troyanskaya Olga O

PLoS computational biology 20100305 3

Genome-scale datasets have been used extensively in model organisms to screen for specific candidates or to predict functions for uncharacterized genes. However, despite the availability of extensive knowledge in model organisms, the planning of genome-scale experiments in poorly studied species is still based on the intuition of experts or heuristic trials. We propose that computational and systematic approaches can be applied to drive the experiment planning process in poorly studied species b ...[more]

PMID: 20221257

Similar Datasets

Project description:Genome-scale datasets have been used extensively in model organisms to screen for specific candidates or to predict functions for uncharacterized genes. However, despite the availability of extensive knowledge in model organisms, the planning of genome-scale experiments in poorly studied species is still based on the intuition of experts or heuristic trials. We propose that computational and systematic approaches can be applied to drive the experiment planning process in poorly studied species based on available data and knowledge in closely related model organisms. In this paper, we suggest a computational strategy for recommending genome-scale experiments based on their capability to interrogate diverse biological processes to enable protein function assignment. To this end, we use the data-rich functional genomics compendium of the model organism to quantify the accuracy of each dataset in predicting each specific biological process and the overlap in such coverage between different datasets. Our approach uses an optimized combination of these quantifications to recommend an ordered list of experiments for accurately annotating most proteins in the poorly studied related organisms to most biological processes, as well as a set of experiments that target each specific biological process. The effectiveness of this experiment- planning system is demonstrated for two related yeast species: the model organism Saccharomyces cerevisiae and the comparatively poorly studied Saccharomyces bayanus. Our system recommended a set of S. bayanus experiments based on an S. cerevisiae microarray data compendium. In silico evaluations estimate that less than 10% of the experiments could achieve similar functional coverage to the whole microarray compendium. This estimation was confirmed by performing the recommended experiments in S. bayanus, therefore significantly reducing the labor devoted to characterize the poorly studied genome. This experiment-planning framework could readily be adapted to the design of other types of large-scale experiments as well as other groups of organisms.

Project description:BackgroundCharacterizing the binding preference of RNA-binding proteins (RBP) is essential for us to understand the interaction between an RBP and its RNA targets, and to decipher the mechanism of post-transcriptional regulation. Experimental methods have been used to generate protein-RNA binding data for a number of RBPs in vivo and in vitro. Utilizing the binding data, a couple of computational methods have been developed to detect the RNA sequence or structure preferences of the RBPs. However, the majority of RBPs have not yet been experimentally characterized and lack RNA binding data. For these poorly studied RBPs, the identification of their binding preferences cannot be performed by most existing computational methods because the experimental binding data are prerequisite to these methods.ResultsHere we propose a new method based on co-evolution to predict the sequence preferences for the poorly studied RBPs, waiving the requirement of their binding data. First, we demonstrate the co-evolutionary relationship between RBPs and their RNA partners. We then present a K-nearest neighbors (KNN) based algorithm to infer the sequence preference of an RBP using only the preference information from its homologous RBPs. By benchmarking against several in vitro and in vivo datasets, our proposed method outperforms the existing alternative which uses the closest neighbor's preference on all the datasets. Moreover, it shows comparable performance with two state-of-the-art methods that require the presence of the experimental binding data. Finally, we demonstrate the usage of this method to infer sequence preferences for novel proteins which have no binding preference information available.ConclusionFor a poorly studied RBP, the current methods used to determine its binding preference need experimental data, which is expensive and time consuming. Therefore, determining RBP's preference is not practical in many situations. This study provides an economic solution to infer the sequence preference of such protein based on the co-evolution. The source codes and related datasets are available at https://github.com/syang11/KNN .

Dataset Information

Systematic planning of genome-scale experiments in poorly studied species.

Publications

Systematic planning of genome-scale experiments in poorly studied species.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets