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Biomedical subjects

Bani Mallick

Publications and source records attributed to Bani Mallick.

3 recordsLinked to original sources

Enrichment analysis in high-throughput genomics - accounting for dependency in the NULL.

Translating the overwhelming amount of data generated in high-throughput genomics experiments into biologically meaningful evidence, which may for example point to a series of biomarkers or hint at a relevant pathway, is a matter of great interest in bioinformatics these days. Genes showing similar experimental profiles, it is hypothesized, share biological mechanisms that if understood could provide clues to the molecular processes leading to pathological events. It is the topic of further study to learn if or how a priori information about the known genes may serve to explain coexpression. One popular method of knowledge discovery in high-throughput genomics experiments, enrichment analysis (EA), seeks to infer if an interesting collection of genes is 'enriched' for a Consortium particular set of a priori Gene Ontology Consortium (GO) classes. For the purposes of statistical testing, the conventional methods offered in EA software implicitly assume independence between the GO classes. Genes may be annotated for more than one biological classification, and therefore the resulting test statistics of enrichment between GO classes can be highly dependent if the overlapping gene sets are relatively large. There is a need to formally determine if conventional EA results are robust to the independence assumption. We derive the exact null distribution for testing enrichment of GO classes by relaxing the independence assumption using well-known statistical theory. In applications with publicly available data sets, our test results are similar to the conventional approach which assumes independence. We argue that the independence assumption is not detrimental.

Data Interpretation, Statistical↗

How many samples are needed to build a classifier: a general sequential approach.

MOTIVATION: The standard paradigm for a classifier design is to obtain a sample of feature-label pairs and then to apply a classification rule to derive a classifier from the sample data. Typically in laboratory situations the sample size is limited by cost, time or availability of sample material. Thus, an investigator may wish to consider a sequential approach in which there is a sufficient number of patients to train a classifier in order to make a sound decision for diagnosis while at the same time keeping the number of patients as small as possible to make the studies affordable. RESULTS: A sequential classification procedure is studied via the martingale central limit theorem. It updates the classification rule at each step and provides stopping criteria to ensure with a certain confidence that at stopping a future subject will have misclassification probability smaller than a predetermined threshold. Simulation studies and applications to microarray data analysis are provided. The procedure possesses several attractive properties: (1) it updates the classification rule sequentially and thus does not rely on distributions of primary measurements from other studies; (2) it assesses the stopping criteria at each sequential step and thus can substantially reduce cost via early stopping; and (3) it is not restricted to any particular classification rule and therefore applies to any parametric or non-parametric method, including feature selection or extraction. AVAILABILITY: R-code for the sequential stopping rule is available at http://stat.tamu.edu/~wfu/microarray/sequential/R-code.html

Algorithms↗

Semiparametric regression modeling with mixtures of Berkson and classical error, with application to fallout from the Nevada test site.

We construct Bayesian methods for semiparametric modeling of a monotonic regression function when the predictors are measured with classical error. Berkson error, or a mixture of the two. Such methods require a distribution for the unobserved (latent) predictor, a distribution we also model semiparametrically. Such combinations of semiparametric methods for the dose response as well as the latent variable distribution have not been considered in the measurement error literature for any form of measurement error. In addition, our methods represent a new approach to those problems where the measurement error combines Berkson and classical components. While the methods are general, we develop them around a specific application, namely, the study of thyroid disease in relation to radiation fallout from the Nevada test site. We use this data to illustrate our methods, which suggest a point estimate (posterior mean) of relative risk at high doses nearly double that of previous analyses but that also suggest much greater uncertainty in the relative risk.

Bayes Theorem↗