4,138 research outputs found
Detecting Gene-Gene Interactions Using a Permutation-Based Random Forest Method
Identifying gene-gene interactions is essential to understand disease susceptibility and to detect genetic architectures underlying complex diseases. Here, we aimed at developing a permutation-based methodology relying on a machine learning method, random forest (RF), to detect gene-gene interactions. Our approach called permuted random forest (pRF) which identified the top interacting single nucleotide polymorphism (SNP) pairs by estimating how much the power of a random forest classification model is influenced by removing pairwise interactions
Statistical methods of SNP data analysis with applications
Various statistical methods important for genetic analysis are considered and
developed. Namely, we concentrate on the multifactor dimensionality reduction,
logic regression, random forests and stochastic gradient boosting. These
methods and their new modifications, e.g., the MDR method with "independent
rule", are used to study the risk of complex diseases such as cardiovascular
ones. The roles of certain combinations of single nucleotide polymorphisms and
external risk factors are examined. To perform the data analysis concerning the
ischemic heart disease and myocardial infarction the supercomputer SKIF
"Chebyshev" of the Lomonosov Moscow State University was employed
Overview of Random Forest Methodology and Practical Guidance with Emphasis on Computational Biology and Bioinformatics
The Random Forest (RF) algorithm by Leo Breiman has become a
standard data analysis tool in bioinformatics. It has shown excellent performance in settings where the number of variables is much larger than the number of observations, can cope with complex interaction structures as well as highly correlated variables and returns measures of variable importance. This paper synthesizes ten years of RF development with emphasis on applications to bioinformatics and computational biology. Special attention is given to practical aspects such as the selection of parameters, available RF implementations, and important pitfalls and biases of RF and its variable importance measures (VIMs). The paper surveys recent developments of the methodology relevant to bioinformatics as well as some representative examples of RF applications in this context and possible directions for future research
Iterative Random Forests to detect predictive and stable high-order interactions
Genomics has revolutionized biology, enabling the interrogation of whole
transcriptomes, genome-wide binding sites for proteins, and many other
molecular processes. However, individual genomic assays measure elements that
interact in vivo as components of larger molecular machines. Understanding how
these high-order interactions drive gene expression presents a substantial
statistical challenge. Building on Random Forests (RF), Random Intersection
Trees (RITs), and through extensive, biologically inspired simulations, we
developed the iterative Random Forest algorithm (iRF). iRF trains a
feature-weighted ensemble of decision trees to detect stable, high-order
interactions with same order of computational cost as RF. We demonstrate the
utility of iRF for high-order interaction discovery in two prediction problems:
enhancer activity in the early Drosophila embryo and alternative splicing of
primary transcripts in human derived cell lines. In Drosophila, among the 20
pairwise transcription factor interactions iRF identifies as stable (returned
in more than half of bootstrap replicates), 80% have been previously reported
as physical interactions. Moreover, novel third-order interactions, e.g.
between Zelda (Zld), Giant (Gt), and Twist (Twi), suggest high-order
relationships that are candidates for follow-up experiments. In human-derived
cells, iRF re-discovered a central role of H3K36me3 in chromatin-mediated
splicing regulation, and identified novel 5th and 6th order interactions,
indicative of multi-valent nucleosomes with specific roles in splicing
regulation. By decoupling the order of interactions from the computational cost
of identification, iRF opens new avenues of inquiry into the molecular
mechanisms underlying genome biology
GOexpress: an R/Bioconductor package for the identification and visualisation of robust gene ontology signatures through supervised learning of gene expression data
Background: Identification of gene expression profiles that differentiate experimental groups is critical for discovery and analysis of key molecular pathways and also for selection of robust diagnostic or prognostic biomarkers. While integration of differential expression statistics has been used to refine gene set enrichment analyses, such approaches are typically limited to single gene lists resulting from simple two-group comparisons or time-series analyses. In contrast, functional class scoring and machine learning approaches provide powerful alternative methods to leverage molecular measurements for pathway analyses, and to compare continuous and multi-level categorical factors. Results: We introduce GOexpress, a software package for scoring and summarising the capacity of gene ontology features to simultaneously classify samples from multiple experimental groups. GOexpress integrates normalised gene expression data (e.g., from microarray and RNA-seq experiments) and phenotypic information of individual samples with gene ontology annotations to derive a ranking of genes and gene ontology terms using a supervised learning approach. The default random forest algorithm allows interactions between all experimental factors, and competitive scoring of expressed genes to evaluate their relative importance in classifying predefined groups of samples. Conclusions: GOexpress enables rapid identification and visualisation of ontology-related gene panels that robustly classify groups of samples and supports both categorical (e.g., infection status, treatment) and continuous (e.g., time-series, drug concentrations) experimental factors. The use of standard Bioconductor extension packages and publicly available gene ontology annotations facilitates straightforward integration of GOexpress within existing computational biology pipelines.Department of Agriculture, Food and the MarineEuropean Commission - Seventh Framework Programme (FP7)Science Foundation IrelandUniversity College Dubli
An Introduction to Recursive Partitioning: Rationale, Application and Characteristics of Classification and Regression Trees, Bagging and Random Forests
Recursive partitioning methods have become popular and widely used tools for nonparametric regression and classification in many scientific fields. Especially random forests, that can deal with large numbers of predictor variables even in the presence of complex interactions, have been applied successfully in genetics, clinical medicine and bioinformatics within the past few years.
High dimensional problems are common not only in genetics, but also in some areas of psychological research, where only few subjects can be measured due to time or cost constraints, yet a large amount of data is generated for each subject. Random forests have been shown to achieve a high prediction accuracy in such applications, and provide descriptive variable importance measures reflecting the impact of each variable in both main effects and interactions.
The aim of this work is to introduce the principles of the standard recursive partitioning methods as well as recent methodological improvements, to illustrate their usage for low and high dimensional data exploration, but also to point out limitations of the methods and potential pitfalls in their practical application.
Application of the methods is illustrated using freely available implementations in the R system for statistical computing
Performance of random forests and logic regression methods using mini-exome sequence data
Machine learning approaches are an attractive option for analyzing large-scale data to detect genetic variants that contribute to variation of a quantitative trait, without requiring specific distributional assumptions. We evaluate two machine learning methods, random forests and logic regression, and compare them to standard simple univariate linear regression, using the Genetic Analysis Workshop 17 mini-exome data. We also apply these methods after collapsing multiple rare variants within genes and within gene pathways. Linear regression and the random forest method performed better when rare variants were collapsed based on genes or gene pathways than when each variant was analyzed separately. Logic regression performed better when rare variants were collapsed based on genes rather than on pathways
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