12,426 research outputs found
Kernel methods in genomics and computational biology
Support vector machines and kernel methods are increasingly popular in
genomics and computational biology, due to their good performance in real-world
applications and strong modularity that makes them suitable to a wide range of
problems, from the classification of tumors to the automatic annotation of
proteins. Their ability to work in high dimension, to process non-vectorial
data, and the natural framework they provide to integrate heterogeneous data
are particularly relevant to various problems arising in computational biology.
In this chapter we survey some of the most prominent applications published so
far, highlighting the particular developments in kernel methods triggered by
problems in biology, and mention a few promising research directions likely to
expand in the future
A novel neural network approach to cDNA microarray image segmentation
This is the post-print version of the Article. The official published version can be accessed from the link below. Copyright @ 2013 Elsevier.Microarray technology has become a great source of information for biologists to understand the workings of DNA which is one of the most complex codes in nature. Microarray images typically contain several thousands of small spots, each of which represents a different gene in the experiment. One of the key steps in extracting information from a microarray image is the segmentation whose aim is to identify which pixels within an image represent which gene. This task is greatly complicated by noise within the image and a wide degree of variation in the values of the pixels belonging to a typical spot. In the past there have been many methods proposed for the segmentation of microarray image. In this paper, a new method utilizing a series of artificial neural networks, which are based on multi-layer perceptron (MLP) and Kohonen networks, is proposed. The proposed method is applied to a set of real-world cDNA images. Quantitative comparisons between the proposed method and commercial software GenePix(Ā®) are carried out in terms of the peak signal-to-noise ratio (PSNR). This method is shown to not only deliver results comparable and even superior to existing techniques but also have a faster run time.This work was funded in part by the National Natural Science Foundation of China under Grants 61174136 and 61104041, the Natural Science Foundation of Jiangsu Province of China under Grant BK2011598, the International Science and Technology Cooperation Project of China under Grant No. 2011DFA12910, the Engineering and Physical Sciences Research Council (EPSRC) of the U.K. under Grant GR/S27658/01, the Royal Society of the U.K., and the Alexander von Humboldt Foundation of Germany
Extracting predictive models from marked-p free-text documents at the Royal Botanic Gardens, Kew, London
In this paper we explore the combination of text-mining, un-supervised and supervised learning to extract predictive models from a corpus of digitised historical floras. These documents deal with the nomenclature, geographical distribution, ecology and comparative morphology of the species of a region. Here we exploit the fact that portions of text in the floras are marked up as different types of trait and habitat. We infer models from these different texts that can predict different habitat-types based upon the traits of plant species. We also integrate plant taxonomy data in order to assist in the validation of our models. We have shown that by clustering text describing the habitat of different floras we can identify a number of important and distinct habitats that are associated with particular families of species along with statistical significance scores. We have also shown that by using these discovered habitat-types as labels for supervised learning we can predict them based upon a subset of traits, identified using wrapper feature selection
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The robust selection of predictive genes via a simple classifier
Identifying genes that direct the mechanism of a disease from expression data is extremely useful in understanding how that mechanism works.
This in turn may lead to better diagnoses and potentially can lead to a cure for that disease. This task becomes extremely challenging when the
data are characterised by only a small number of samples and a high number of dimensions, as it is often the case with gene expression data.
Motivated by this challenge, we present a general framework that focuses on simplicity and data perturbation. These are the keys for the robust
identification of the most predictive features in such data. Within this framework, we propose a simple selective naĀØıve Bayes classifier discovered using a global search technique, and combine it with data perturbation to
increase its robustness to small sample sizes.
An extensive validation of the method was carried out using two applied datasets from the field of microarrays and a simulated dataset, all
confounded by small sample sizes and high dimensionality. The method has been shown capable of identifying genes previously confirmed or associated with prostate cancer and viral infections
Comparative analysis of Salmonella susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defense network
peer-reviewedChlorhexidine is one of the most widely used biocides in health and agricultural settings as well as in the modern food industry. It is a cationic biocide of the biguanide class. Details of its mechanism of action are largely unknown. The frequent use of chlorhexidine has been questioned recently, amidst concerns that an overuse of this compound may select for bacteria displaying an altered susceptibility to antimicrobials, including clinically important anti-bacterial agents. We generated a Salmonella enterica serovar Typhimurium isolate (ST24CHX) that exhibited a high-level tolerant phenotype to chlorhexidine, following several rounds of in vitro selection, using sub-lethal concentrations of the biocide. This mutant showed altered suceptibility to a panel of clinically important antimicrobial compounds. Here we describe a genomic, transcriptomic, proteomic, and phenotypic analysis of the chlorhexidine tolerant S. Typhimurium compared with its isogenic sensitive progenitor. Results from this study describe a chlorhexidine defense network that functions in both the reference chlorhexidine sensitive isolate and the tolerant mutant. The defense network involved multiple cell targets including those associated with the synthesis and modification of the cell wall, the SOS response, virulence, and a shift in cellular metabolism toward anoxic pathways, some of which were regulated by CreB and Fur. In addition, results indicated that chlorhexidine tolerance was associated with more extensive modifications of the same cellular processes involved in this proposed network, as well as a divergent defense response involving the up-regulation of additional targets such as the flagellar apparatus and an altered cellular phosphate metabolism. These data show that sub-lethal concentrations of chlorhexidine induce distinct changes in exposed Salmonella, and our findings provide insights into the mechanisms of action and tolerance to this biocidal agent.Department of Agriculture, Food and the Marin
Comparison of Clustering Methods for Time Course Genomic Data: Applications to Aging Effects
Time course microarray data provide insight about dynamic biological
processes. While several clustering methods have been proposed for the analysis
of these data structures, comparison and selection of appropriate clustering
methods are seldom discussed. We compared probabilistic based clustering
methods and distance based clustering methods for time course microarray
data. Among probabilistic methods, we considered: smoothing spline clustering
also known as model based functional data analysis (MFDA), functional
clustering models for sparsely sampled data (FCM) and model-based clustering
(MCLUST). Among distance based methods, we considered: weighted gene
co-expression network analysis (WGCNA), clustering with dynamic time warping
distance (DTW) and clustering with autocorrelation based distance (ACF). We
studied these algorithms in both simulated settings and case study data. Our
investigations showed that FCM performed very well when gene curves were short
and sparse. DTW and WGCNA performed well when gene curves were medium or long
( observations). SSC performed very well when there were clusters of gene
curves similar to one another. Overall, ACF performed poorly in these
applications. In terms of computation time, FCM, SSC and DTW were considerably
slower than MCLUST and WGCNA. WGCNA outperformed MCLUST by generating more
accurate and biological meaningful clustering results. WGCNA and MCLUST are the
best methods among the 6 methods compared, when performance and computation
time are both taken into account. WGCNA outperforms MCLUST, but MCLUST provides
model based inference and uncertainty measure of clustering results
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