35,954 research outputs found
Genomic data sampling and its effect on classification performance assessment
BACKGROUND: Supervised classification is fundamental in bioinformatics. Machine learning models, such as neural networks, have been applied to discover genes and expression patterns. This process is achieved by implementing training and test phases. In the training phase, a set of cases and their respective labels are used to build a classifier. During testing, the classifier is used to predict new cases. One approach to assessing its predictive quality is to estimate its accuracy during the test phase. Key limitations appear when dealing with small-data samples. This paper investigates the effect of data sampling techniques on the assessment of neural network classifiers. RESULTS: Three data sampling techniques were studied: Cross-validation, leave-one-out, and bootstrap. These methods are designed to reduce the bias and variance of small-sample estimations. Two prediction problems based on small-sample sets were considered: Classification of microarray data originating from a leukemia study and from small, round blue-cell tumours. A third problem, the prediction of splice-junctions, was analysed to perform comparisons. Different accuracy estimations were produced for each problem. The variations are accentuated in the small-data samples. The quality of the estimates depends on the number of train-test experiments and the amount of data used for training the networks. CONCLUSION: The predictive quality assessment of biomolecular data classifiers depends on the data size, sampling techniques and the number of train-test experiments. Conservative and optimistic accuracy estimations can be obtained by applying different methods. Guidelines are suggested to select a sampling technique according to the complexity of the prediction problem under consideration
Bayesian Approximate Kernel Regression with Variable Selection
Nonlinear kernel regression models are often used in statistics and machine
learning because they are more accurate than linear models. Variable selection
for kernel regression models is a challenge partly because, unlike the linear
regression setting, there is no clear concept of an effect size for regression
coefficients. In this paper, we propose a novel framework that provides an
effect size analog of each explanatory variable for Bayesian kernel regression
models when the kernel is shift-invariant --- for example, the Gaussian kernel.
We use function analytic properties of shift-invariant reproducing kernel
Hilbert spaces (RKHS) to define a linear vector space that: (i) captures
nonlinear structure, and (ii) can be projected onto the original explanatory
variables. The projection onto the original explanatory variables serves as an
analog of effect sizes. The specific function analytic property we use is that
shift-invariant kernel functions can be approximated via random Fourier bases.
Based on the random Fourier expansion we propose a computationally efficient
class of Bayesian approximate kernel regression (BAKR) models for both
nonlinear regression and binary classification for which one can compute an
analog of effect sizes. We illustrate the utility of BAKR by examining two
important problems in statistical genetics: genomic selection (i.e. phenotypic
prediction) and association mapping (i.e. inference of significant variants or
loci). State-of-the-art methods for genomic selection and association mapping
are based on kernel regression and linear models, respectively. BAKR is the
first method that is competitive in both settings.Comment: 22 pages, 3 figures, 3 tables; theory added; new simulations
presented; references adde
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
High performance computation of landscape genomic models integrating local indices of spatial association
Since its introduction, landscape genomics has developed quickly with the
increasing availability of both molecular and topo-climatic data. The current
challenges of the field mainly involve processing large numbers of models and
disentangling selection from demography. Several methods address the latter,
either by estimating a neutral model from population structure or by inferring
simultaneously environmental and demographic effects. Here we present
Samada, an integrated approach to study signatures of local adaptation,
providing rapid processing of whole genome data and enabling assessment of
spatial association using molecular markers. Specifically, candidate loci to
adaptation are identified by automatically assessing genome-environment
associations. In complement, measuring the Local Indicators of Spatial
Association (LISA) for these candidate loci allows to detect whether similar
genotypes tend to gather in space, which constitutes a useful indication of the
possible kinship relationship between individuals. In this paper, we also
analyze SNP data from Ugandan cattle to detect signatures of local adaptation
with Samada, BayEnv, LFMM and an outlier method (FDIST approach in
Arlequin) and compare their results. Samada is an open source software
for Windows, Linux and MacOS X available at \url{http://lasig.epfl.ch/sambada}Comment: 1 figure in text, 1 figure in supplementary material The structure of
the article was modified and some explanations were updated. The methods and
results presented are the same as in the previous versio
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Meta-analysis of massively parallel reporter assays enables prediction of regulatory function across cell types.
Deciphering the potential of noncoding loci to influence gene regulation has been the subject of intense research, with important implications in understanding genetic underpinnings of human diseases. Massively parallel reporter assays (MPRAs) can measure regulatory activity of thousands of DNA sequences and their variants in a single experiment. With increasing number of publically available MPRA data sets, one can now develop data-driven models which, given a DNA sequence, predict its regulatory activity. Here, we performed a comprehensive meta-analysis of several MPRA data sets in a variety of cellular contexts. We first applied an ensemble of methods to predict MPRA output in each context and observed that the most predictive features are consistent across data sets. We then demonstrate that predictive models trained in one cellular context can be used to predict MPRA output in another, with loss of accuracy attributed to cell-type-specific features. Finally, we show that our approach achieves top performance in the Fifth Critical Assessment of Genome Interpretation "Regulation Saturation" Challenge for predicting effects of single-nucleotide variants. Overall, our analysis provides insights into how MPRA data can be leveraged to highlight functional regulatory regions throughout the genome and can guide effective design of future experiments by better prioritizing regions of interest
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VarSight: prioritizing clinically reported variants with binary classification algorithms.
BackgroundWhen applying genomic medicine to a rare disease patient, the primary goal is to identify one or more genomic variants that may explain the patient's phenotypes. Typically, this is done through annotation, filtering, and then prioritization of variants for manual curation. However, prioritization of variants in rare disease patients remains a challenging task due to the high degree of variability in phenotype presentation and molecular source of disease. Thus, methods that can identify and/or prioritize variants to be clinically reported in the presence of such variability are of critical importance.MethodsWe tested the application of classification algorithms that ingest variant annotations along with phenotype information for predicting whether a variant will ultimately be clinically reported and returned to a patient. To test the classifiers, we performed a retrospective study on variants that were clinically reported to 237 patients in the Undiagnosed Diseases Network.ResultsWe treated the classifiers as variant prioritization systems and compared them to four variant prioritization algorithms and two single-measure controls. We showed that the trained classifiers outperformed all other tested methods with the best classifiers ranking 72% of all reported variants and 94% of reported pathogenic variants in the top 20.ConclusionsWe demonstrated how freely available binary classification algorithms can be used to prioritize variants even in the presence of real-world variability. Furthermore, these classifiers outperformed all other tested methods, suggesting that they may be well suited for working with real rare disease patient datasets
miSTAR : miRNA target prediction through modeling quantitative and qualitative miRNA binding site information in a stacked model structure
In microRNA (miRNA) target prediction, typically two levels of information need to be modeled: the number of potential miRNA binding sites present in a target mRNA and the genomic context of each individual site. Single model structures insufficiently cope with this complex training data structure, consisting of feature vectors of unequal length as a consequence of the varying number of miRNA binding sites in different mRNAs. To circumvent this problem, we developed a two-layered, stacked model, in which the influence of binding site context is separately modeled. Using logistic regression and random forests, we applied the stacked model approach to a unique data set of 7990 probed miRNA-mRNA interactions, hereby including the largest number of miRNAs in model training to date. Compared to lower-complexity models, a particular stacked model, named miSTAR (miRNA stacked model target prediction; www.mi-star.org), displays a higher general performance and precision on top scoring predictions. More importantly, our model outperforms published and widely used miRNA target prediction algorithms. Finally, we highlight flaws in cross-validation schemes for evaluation of miRNA target prediction models and adopt a more fair and stringent approach
Classifying pairs with trees for supervised biological network inference
Networks are ubiquitous in biology and computational approaches have been
largely investigated for their inference. In particular, supervised machine
learning methods can be used to complete a partially known network by
integrating various measurements. Two main supervised frameworks have been
proposed: the local approach, which trains a separate model for each network
node, and the global approach, which trains a single model over pairs of nodes.
Here, we systematically investigate, theoretically and empirically, the
exploitation of tree-based ensemble methods in the context of these two
approaches for biological network inference. We first formalize the problem of
network inference as classification of pairs, unifying in the process
homogeneous and bipartite graphs and discussing two main sampling schemes. We
then present the global and the local approaches, extending the later for the
prediction of interactions between two unseen network nodes, and discuss their
specializations to tree-based ensemble methods, highlighting their
interpretability and drawing links with clustering techniques. Extensive
computational experiments are carried out with these methods on various
biological networks that clearly highlight that these methods are competitive
with existing methods.Comment: 22 page
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