5,800 research outputs found
Improved Microarray-Based Decision Support with Graph Encoded Interactome Data
In the past, microarray studies have been criticized due to noise and the limited overlap between gene signatures. Prior biological knowledge should therefore be incorporated as side information in models based on gene expression data to improve the accuracy of diagnosis and prognosis in cancer. As prior knowledge, we investigated interaction and pathway information from the human interactome on different aspects of biological systems. By exploiting the properties of kernel methods, relations between genes with similar functions but active in alternative pathways could be incorporated in a support vector machine classifier based on spectral graph theory. Using 10 microarray data sets, we first reduced the number of data sources relevant for multiple cancer types and outcomes. Three sources on metabolic pathway information (KEGG), protein-protein interactions (OPHID) and miRNA-gene targeting (microRNA.org) outperformed the other sources with regard to the considered class of models. Both fixed and adaptive approaches were subsequently considered to combine the three corresponding classifiers. Averaging the predictions of these classifiers performed best and was significantly better than the model based on microarray data only. These results were confirmed on 6 validation microarray sets, with a significantly improved performance in 4 of them. Integrating interactome data thus improves classification of cancer outcome for the investigated microarray technologies and cancer types. Moreover, this strategy can be incorporated in any kernel method or non-linear version of a non-kernel method
Integrative analysis of large-scale biological data sets
We present two novel web-applications for microarray and gene/protein set analysis, ArrayMining.net and TopoGSA. These bioinformatics tools use integrative analysis methods, including ensemble and consensus machine learning techniques, as well as modular combinations of different analysis types, to extract new biological insights from experimental transcriptomics and proteomics data. They enable researchers to combine related algorithms and datasets to increase the robustness and accuracy of statistical analyses and exploit synergies of different computational methods, ranging from statistical learning to optimization and topological network analysis
A critical evaluation of network and pathway based classifiers for outcome prediction in breast cancer
Recently, several classifiers that combine primary tumor data, like gene
expression data, and secondary data sources, such as protein-protein
interaction networks, have been proposed for predicting outcome in breast
cancer. In these approaches, new composite features are typically constructed
by aggregating the expression levels of several genes. The secondary data
sources are employed to guide this aggregation. Although many studies claim
that these approaches improve classification performance over single gene
classifiers, the gain in performance is difficult to assess. This stems mainly
from the fact that different breast cancer data sets and validation procedures
are employed to assess the performance. Here we address these issues by
employing a large cohort of six breast cancer data sets as benchmark set and by
performing an unbiased evaluation of the classification accuracies of the
different approaches. Contrary to previous claims, we find that composite
feature classifiers do not outperform simple single gene classifiers. We
investigate the effect of (1) the number of selected features; (2) the specific
gene set from which features are selected; (3) the size of the training set and
(4) the heterogeneity of the data set on the performance of composite feature
and single gene classifiers. Strikingly, we find that randomization of
secondary data sources, which destroys all biological information in these
sources, does not result in a deterioration in performance of composite feature
classifiers. Finally, we show that when a proper correction for gene set size
is performed, the stability of single gene sets is similar to the stability of
composite feature sets. Based on these results there is currently no reason to
prefer prognostic classifiers based on composite features over single gene
classifiers for predicting outcome in breast cancer
Inverse Projection Representation and Category Contribution Rate for Robust Tumor Recognition
Sparse representation based classification (SRC) methods have achieved
remarkable results. SRC, however, still suffer from requiring enough training
samples, insufficient use of test samples and instability of representation. In
this paper, a stable inverse projection representation based classification
(IPRC) is presented to tackle these problems by effectively using test samples.
An IPR is firstly proposed and its feasibility and stability are analyzed. A
classification criterion named category contribution rate is constructed to
match the IPR and complete classification. Moreover, a statistical measure is
introduced to quantify the stability of representation-based classification
methods. Based on the IPRC technique, a robust tumor recognition framework is
presented by interpreting microarray gene expression data, where a two-stage
hybrid gene selection method is introduced to select informative genes.
Finally, the functional analysis of candidate's pathogenicity-related genes is
given. Extensive experiments on six public tumor microarray gene expression
datasets demonstrate the proposed technique is competitive with
state-of-the-art methods.Comment: 14 pages, 19 figures, 10 table
Machine Learning and Integrative Analysis of Biomedical Big Data.
Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues
A systems biology analysis of brain microvascular endothelial cell lipotoxicity.
BackgroundNeurovascular inflammation is associated with a number of neurological diseases including vascular dementia and Alzheimer's disease, which are increasingly important causes of morbidity and mortality around the world. Lipotoxicity is a metabolic disorder that results from accumulation of lipids, particularly fatty acids, in non-adipose tissue leading to cellular dysfunction, lipid droplet formation, and cell death.ResultsOur studies indicate for the first time that the neurovascular circulation also can manifest lipotoxicity, which could have major effects on cognitive function. The penetration of integrative systems biology approaches is limited in this area of research, which reduces our capacity to gain an objective insight into the signal transduction and regulation dynamics at a systems level. To address this question, we treated human microvascular endothelial cells with triglyceride-rich lipoprotein (TGRL) lipolysis products and then we used genome-wide transcriptional profiling to obtain transcript abundances over four conditions. We then identified regulatory genes and their targets that have been differentially expressed through analysis of the datasets with various statistical methods. We created a functional gene network by exploiting co-expression observations through a guilt-by-association assumption. Concomitantly, we used various network inference algorithms to identify putative regulatory interactions and we integrated all predictions to construct a consensus gene regulatory network that is TGRL lipolysis product specific.ConclusionSystem biology analysis has led to the validation of putative lipid-related targets and the discovery of several genes that may be implicated in lipotoxic-related brain microvascular endothelial cell responses. Here, we report that activating transcription factors 3 (ATF3) is a principal regulator of TGRL lipolysis products-induced gene expression in human brain microvascular endothelial cell
Tellipsoid: Exploiting inter-gene correlation for improved detection of differential gene expression
Motivation: Algorithms for differential analysis of microarray data are vital
to modern biomedical research. Their accuracy strongly depends on effective
treatment of inter-gene correlation. Correlation is ordinarily accounted for in
terms of its effect on significance cut-offs. In this paper it is shown that
correlation can, in fact, be exploited {to share information across tests},
which, in turn, can increase statistical power.
Results: Vastly and demonstrably improved differential analysis approaches
are the result of combining identifiability (the fact that in most microarray
data sets, a large proportion of genes can be identified a priori as
non-differential) with optimization criteria that incorporate correlation. As a
special case, we develop a method which builds upon the widely used two-sample
t-statistic based approach and uses the Mahalanobis distance as an optimality
criterion. Results on the prostate cancer data of Singh et al. (2002) suggest
that the proposed method outperforms all published approaches in terms of
statistical power.
Availability: The proposed algorithm is implemented in MATLAB and in R. The
software, called Tellipsoid, and relevant data sets are available at
http://www.egr.msu.edu/~desaikeyComment: 19 pages, Submitted to Bioinformatic
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