6,158 research outputs found
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
An evaluation of DNA-damage response and cell-cycle pathways for breast cancer classification
Accurate subtyping or classification of breast cancer is important for
ensuring proper treatment of patients and also for understanding the molecular
mechanisms driving this disease. While there have been several gene signatures
proposed in the literature to classify breast tumours, these signatures show
very low overlaps, different classification performance, and not much relevance
to the underlying biology of these tumours. Here we evaluate DNA-damage
response (DDR) and cell cycle pathways, which are critical pathways implicated
in a considerable proportion of breast tumours, for their usefulness and
ability in breast tumour subtyping. We think that subtyping breast tumours
based on these two pathways could lead to vital insights into molecular
mechanisms driving these tumours. Here, we performed a systematic evaluation of
DDR and cell-cycle pathways for subtyping of breast tumours into the five known
intrinsic subtypes. Homologous Recombination (HR) pathway showed the best
performance in subtyping breast tumours, indicating that HR genes are strongly
involved in all breast tumours. Comparisons of pathway based signatures and two
standard gene signatures supported the use of known pathways for breast tumour
subtyping. Further, the evaluation of these standard gene signatures showed
that breast tumour subtyping, prognosis and survival estimation are all closely
related. Finally, we constructed an all-inclusive super-signature by combining
(union of) all genes and performing a stringent feature selection, and found it
to be reasonably accurate and robust in classification as well as prognostic
value. Adopting DDR and cell cycle pathways for breast tumour subtyping
achieved robust and accurate breast tumour subtyping, and constructing a
super-signature which contains feature selected mix of genes from these
molecular pathways as well as clinical aspects is valuable in clinical
practice.Comment: 28 pages, 7 figures, 6 table
Gene ranking and biomarker discovery under correlation
Biomarker discovery and gene ranking is a standard task in genomic high
throughput analysis. Typically, the ordering of markers is based on a
stabilized variant of the t-score, such as the moderated t or the SAM
statistic. However, these procedures ignore gene-gene correlations, which may
have a profound impact on the gene orderings and on the power of the subsequent
tests.
We propose a simple procedure that adjusts gene-wise t-statistics to take
account of correlations among genes. The resulting correlation-adjusted
t-scores ("cat" scores) are derived from a predictive perspective, i.e. as a
score for variable selection to discriminate group membership in two-class
linear discriminant analysis. In the absence of correlation the cat score
reduces to the standard t-score. Moreover, using the cat score it is
straightforward to evaluate groups of features (i.e. gene sets). For
computation of the cat score from small sample data we propose a shrinkage
procedure. In a comparative study comprising six different synthetic and
empirical correlation structures we show that the cat score improves estimation
of gene orderings and leads to higher power for fixed true discovery rate, and
vice versa. Finally, we also illustrate the cat score by analyzing metabolomic
data.
The shrinkage cat score is implemented in the R package "st" available from
URL http://cran.r-project.org/web/packages/st/Comment: 18 pages, 5 figures, 1 tabl
An integrated method for cancer classification and rule extraction from microarray data
Different microarray techniques recently have been successfully used to investigate useful information for cancer diagnosis at the gene expression level due to their ability to measure thousands of gene expression levels in a massively parallel way. One important issue is to improve classification performance of microarray data. However, it would be ideal that influential genes and even interpretable rules can be explored at the same time to offer biological insight
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