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Exploiting dependencies of pairwise comparison outcomes to predict patterns of gene response.

ABSTRACT: BACKGROUND: The analysis of gene expression has played an important role in medical and bioinformatics research. Although it is known that a large number of samples is needed to determine the patterns of gene expression accurately, practical designs of gene expression studies occasionally have insufficient numbers of samples, making it difficult to ascertain true response patterns of variantly expressed genes. RESULTS: We describe an approach to cope with the challenge of predicting true orders of gene response to treatments. We show that true patterns of gene response must be orderable sets. In experiments with few samples, we modify the conventional pairwise comparison tests and increase the significance level ? intelligently to deduce orderable patterns, which are most likely true orders of gene response. Additionally, motivated by the fact that a gene can be involved in multiple biological functions, our method further resamples experimental replicates and predicts multiple response patterns for each gene. CONCLUSIONS: This method can be useful in designing cost-effective experiments with small sample sizes. Patterns of highly-variantly expressed genes can be predicted by varying ? intelligently. Furthermore, clusters are labeled meaningfully with patterns that describe precisely how genes in such clusters respond to treatments.

SUBMITTER: Vo NS

PROVIDER: S-EPMC4251046 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Exploiting dependencies of pairwise comparison outcomes to predict patterns of gene response.

Vo Nam S NS Phan Vinhthuy V

BMC bioinformatics 20141021

<h4>Background</h4>The analysis of gene expression has played an important role in medical and bioinformatics research. Although it is known that a large number of samples is needed to determine the patterns of gene expression accurately, practical designs of gene expression studies occasionally have insufficient numbers of samples, making it difficult to ascertain true response patterns of variantly expressed genes.<h4>Results</h4>We describe an approach to cope with the challenge of predicting ...[more]

PMID: 25350806

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Project description:MotivationIn recent years, vast advances in biomedical technologies and comprehensive sequencing have revealed the genomic landscape of common forms of human cancer in unprecedented detail. The broad heterogeneity of the disease calls for rapid development of personalized therapies. Translating the readily available genomic data into useful knowledge that can be applied in the clinic remains a challenge. Computational methods are needed to aid these efforts by robustly analyzing genome-scale data from distinct experimental platforms for prioritization of targets and treatments.ResultsWe propose a novel, biologically motivated, Bayesian multitask approach, which explicitly models gene-centric dependencies across multiple and distinct genomic platforms. We introduce a gene-wise prior and present a fully Bayesian formulation of a group factor analysis model. In supervised prediction applications, our multitask approach leverages similarities in response profiles of groups of drugs that are more likely to be related to true biological signal, which leads to more robust performance and improved generalization ability. We evaluate the performance of our method on molecularly characterized collections of cell lines profiled against two compound panels, namely the Cancer Cell Line Encyclopedia and the Cancer Therapeutics Response Portal. We demonstrate that accounting for the gene-centric dependencies enables leveraging information from multi-omic input data and improves prediction and feature selection performance. We further demonstrate the applicability of our method in an unsupervised dimensionality reduction application by inferring genes essential to tumorigenesis in the pancreatic ductal adenocarcinoma and lung adenocarcinoma patient cohorts from The Cancer Genome Atlas.Availability and implementation: The code for this work is available at https://github.com/olganikolova/gbgfa.Contact: nikolova@ohsu.edu or margolin@ohsu.edu.Supplementary informationSupplementary data are available at Bioinformatics online.

Project description:BackgroundConventional pairwise sequence comparison software algorithms are being used to process much larger datasets than they were originally designed for. This can result in processing bottlenecks that limit software capabilities or prevent full use of the available hardware resources. Overcoming the barriers that limit the efficient computational analysis of large biological sequence datasets by retrofitting existing algorithms or by creating new applications represents a major challenge for the bioinformatics community.ResultsWe have developed C libraries for pairwise sequence comparison within diverse architectures, ranging from commodity systems to high performance and cloud computing environments. Exhaustive tests were performed using different datasets of closely- and distantly-related sequences that span from small viral genomes to large mammalian chromosomes. The tests demonstrated that our solution is capable of generating high quality results with a linear-time response and controlled memory consumption, being comparable or faster than the current state-of-the-art methods.ConclusionsWe have addressed the problem of pairwise and all-versus-all comparison of large sequences in general, greatly increasing the limits on input data size. The approach described here is based on a modular out-of-core strategy that uses secondary storage to avoid reaching memory limits during the identification of High-scoring Segment Pairs (HSPs) between the sequences under comparison. Software engineering concepts were applied to avoid intermediate result re-calculation, to minimise the performance impact of input/output (I/O) operations and to modularise the process, thus enhancing application flexibility and extendibility. Our computationally-efficient approach allows tasks such as the massive comparison of complete genomes, evolutionary event detection, the identification of conserved synteny blocks and inter-genome distance calculations to be performed more effectively.

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Exploiting dependencies of pairwise comparison outcomes to predict patterns of gene response.

Publications

Exploiting dependencies of pairwise comparison outcomes to predict patterns of gene response.

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