24,826 research outputs found
Stable Feature Selection for Biomarker Discovery
Feature selection techniques have been used as the workhorse in biomarker
discovery applications for a long time. Surprisingly, the stability of feature
selection with respect to sampling variations has long been under-considered.
It is only until recently that this issue has received more and more attention.
In this article, we review existing stable feature selection methods for
biomarker discovery using a generic hierarchal framework. We have two
objectives: (1) providing an overview on this new yet fast growing topic for a
convenient reference; (2) categorizing existing methods under an expandable
framework for future research and development
An Integrated, Module-based Biomarker Discovery Framework
Identification of biomarkers that contribute to complex human disorders is a principal and challenging task in computational biology. Prognostic biomarkers are useful for risk assessment of disease progression and patient stratification. Since treatment plans often hinge on patient stratification, better disease subtyping has the potential to significantly improve survival for patients. Additionally, a thorough understanding of the roles of biomarkers in cancer pathways facilitates insights into complex disease formation, and provides potential druggable targets in the pathways.
Many statistical methods have been applied toward biomarker discovery, often combining feature selection with classification methods. Traditional approaches are mainly concerned with statistical significance and fail to consider the clinical relevance of the selected biomarkers. Two additional problems impede meaningful biomarker discovery: gene multiplicity (several maximally predictive solutions exist) and instability (inconsistent gene sets from different experiments or cross validation runs).
Motivated by a need for more biologically informed, stable biomarker discovery method, I introduce an integrated module-based biomarker discovery framework for analyzing high- throughput genomic disease data. The proposed framework addresses the aforementioned challenges in three components. First, a recursive spectral clustering algorithm specifically
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tailored toward high-dimensional, heterogeneous data (ReKS) is developed to partition genes into clusters that are treated as single entities for subsequent analysis. Next, the problems of gene multiplicity and instability are addressed through a group variable selection algorithm (T-ReCS) based on local causal discovery methods. Guided by the tree-like partition created from the clustering algorithm, this algorithm selects gene clusters that are predictive of a clinical outcome. We demonstrate that the group feature selection method facilitate the discovery of biologically relevant genes through their association with a statistically predictive driver. Finally, we elucidate the biological relevance of the biomarkers by leveraging available prior information to identify regulatory relationships between genes and between clusters, and deliver the information in the form of a user-friendly web server, mirConnX
EFSIS: Ensemble Feature Selection Integrating Stability
Ensemble learning that can be used to combine the predictions from multiple
learners has been widely applied in pattern recognition, and has been reported
to be more robust and accurate than the individual learners. This ensemble
logic has recently also been more applied in feature selection. There are
basically two strategies for ensemble feature selection, namely data
perturbation and function perturbation. Data perturbation performs feature
selection on data subsets sampled from the original dataset and then selects
the features consistently ranked highly across those data subsets. This has
been found to improve both the stability of the selector and the prediction
accuracy for a classifier. Function perturbation frees the user from having to
decide on the most appropriate selector for any given situation and works by
aggregating multiple selectors. This has been found to maintain or improve
classification performance. Here we propose a framework, EFSIS, combining these
two strategies. Empirical results indicate that EFSIS gives both high
prediction accuracy and stability.Comment: 20 pages, 3 figure
Inferential stability in systems biology
The modern biological sciences are fraught with statistical difficulties. Biomolecular
stochasticity, experimental noise, and the “large p, small n” problem all contribute to
the challenge of data analysis. Nevertheless, we routinely seek to draw robust, meaningful
conclusions from observations. In this thesis, we explore methods for assessing
the effects of data variability upon downstream inference, in an attempt to quantify and
promote the stability of the inferences we make.
We start with a review of existing methods for addressing this problem, focusing upon the
bootstrap and similar methods. The key requirement for all such approaches is a statistical
model that approximates the data generating process.
We move on to consider biomarker discovery problems. We present a novel algorithm for
proposing putative biomarkers on the strength of both their predictive ability and the stability
with which they are selected. In a simulation study, we find our approach to perform
favourably in comparison to strategies that select on the basis of predictive performance
alone.
We then consider the real problem of identifying protein peak biomarkers for HAM/TSP,
an inflammatory condition of the central nervous system caused by HTLV-1 infection.
We apply our algorithm to a set of SELDI mass spectral data, and identify a number of
putative biomarkers. Additional experimental work, together with known results from the
literature, provides corroborating evidence for the validity of these putative biomarkers.
Having focused on static observations, we then make the natural progression to time
course data sets. We propose a (Bayesian) bootstrap approach for such data, and then
apply our method in the context of gene network inference and the estimation of parameters
in ordinary differential equation models. We find that the inferred gene networks
are relatively unstable, and demonstrate the importance of finding distributions of ODE
parameter estimates, rather than single point estimates
The influence of feature selection methods on accuracy, stability and interpretability of molecular signatures
Motivation: Biomarker discovery from high-dimensional data is a crucial
problem with enormous applications in biology and medicine. It is also
extremely challenging from a statistical viewpoint, but surprisingly few
studies have investigated the relative strengths and weaknesses of the plethora
of existing feature selection methods. Methods: We compare 32 feature selection
methods on 4 public gene expression datasets for breast cancer prognosis, in
terms of predictive performance, stability and functional interpretability of
the signatures they produce. Results: We observe that the feature selection
method has a significant influence on the accuracy, stability and
interpretability of signatures. Simple filter methods generally outperform more
complex embedded or wrapper methods, and ensemble feature selection has
generally no positive effect. Overall a simple Student's t-test seems to
provide the best results. Availability: Code and data are publicly available at
http://cbio.ensmp.fr/~ahaury/
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