Searcharxiv⌕ Search

arXiv subjects

Wentian Li

Publications and source records attributed to Wentian Li.

47 records · Page 3Linked to original sources

Extreme Value Distribution Based Gene Selection Criteria for Discriminant Microarray Data Analysis Using Logistic Regression

One important issue commonly encountered in the analysis of microarray data is to decide which and how many genes should be selected for further studies. For discriminant microarray data analyses based on statistical models, such as the logistic regression models, gene selection can be accomplished by a comparison of the maximum likelihood of the model given the real data, $\hat{L}(D|M)$, and the expected maximum likelihood of the model given an ensemble of surrogate data with randomly permuted label, $\hat{L}(D_0|M)$. Typically, the computational burden for obtaining $\hat{L}(D_0|M)$ is immense, often exceeding the limits of computing available resources by orders of magnitude. Here, we propose an approach that circumvents such heavy computations by mapping the simulation problem to an extreme-value problem. We present the derivation of an asymptotic distribution of the extreme-value as well as its mean, median, and variance. Using this distribution, we propose two gene selection criteria, and we apply them to two microarray datasets and three classification tasks for illustration.

q-bio.QM↗

Isochores Merit the Prefix 'Iso'

The isochore concept in human genome sequence was challenged in an analysis by the International Human Genome Sequencing Consortium (IHGSC). We argue here that a statement in IGHSC analysis concerning the existence of isochore is incorrect, because it had applied an inappropriate statistical test. To test the existence of isochores should be equivalent to a test of homogeneity of windowed GC%. The statistical test applied in the IHGSC's analysis, the binomial test, is however a test of a sequence being random on the base level. For testing the existence of isochore, or homogeneity in GC%, we propose to use another statistical test: the analysis of variance (ANOVA). It can be shown that DNA sequences that are rejected by binomial test may not be rejected by the ANOVA test.

physics.bio-ph↗

Simplifying the mosaic description of DNA sequences

By using the Jensen-Shannon divergence, genomic DNA can be divided into compositionally distinct domains through a standard recursive segmentation procedure. Each domain, while significantly different from its neighbours, may however share compositional similarity with one or more distant (non--neighbouring) domains. We thus obtain a coarse--grained description of the given DNA string in terms of a smaller set of distinct domain labels. This yields a minimal domain description of a given DNA sequence, significantly reducing its organizational complexity. This procedure gives a new means of evaluating genomic complexity as one examines organisms ranging from bacteria to human. The mosaic organization of DNA sequences could have originated from the insertion of fragments of one genome (the parasite) inside another (the host), and we present numerical experiments that are suggestive of this scenario.

physics.bio-ph↗

How Many Genes Are Needed for a Discriminant Microarray Data Analysis ?

The analysis of the leukemia data from Whitehead/MIT group is a discriminant analysis (also called a supervised learning). Among thousands of genes whose expression levels are measured, not all are needed for discriminant analysis: a gene may either not contribute to the separation of two types of tissues/cancers, or it may be redundant because it is highly correlated with other genes. There are two theoretical frameworks in which variable selection (or gene selection in our case) can be addressed. The first is model selection, and the second is model averaging. We have carried out model selection using Akaike information criterion and Bayesian information criterion with logistic regression (discrimination, prediction, or classification) to determine the number of genes that provide the best model. These model selection criteria set upper limits of 22-25 and 12-13 genes for this data set with 38 samples, and the best model consists of only one (no.4847, zyxin) or two genes. We have also carried out model averaging over the best single-gene logistic predictors using three different weights: maximized likelihood, prediction rate on training set, and equal weight. We have observed that the performance of most of these weighted predictors on the testing set is gradually reduced as more genes are included, but a clear cutoff that separates good and bad prediction performance is not found.

physics.bio-ph↗

Zipf's Law in Importance of Genes for Cancer Classification Using Microarray Data

Microarray data consists of mRNA expression levels of thousands of genes under certain conditions. A difference in the expression level of a gene at two different conditions/phenotypes, such as cancerous versus non-cancerous, one subtype of cancer versus another, before versus after a drug treatment, is indicative of the relevance of that gene to the difference of the high-level phenotype. Each gene can be ranked by its ability to distinguish the two conditions. We study how the single-gene classification ability decreases with its rank (a Zipf's plot). Power-law function in the Zipf's plot is observed for the four microarray datasets obtained from various cancer studies. This power-law behavior in the Zipf's plot is reminiscent of similar power-law curves in other natural and social phenomena (Zipf's law). However, due to our choice of the measure of importance in classification ability, i.e., the maximized likelihood in a logistic regression, the exponent of the power-law function is a function of the sample size, instead of a fixed value close to 1 for a typical example of Zipf's law. The presence of this power-law behavior is important for deciding the number of genes to be used for a discriminant microarray data analysis.

physics.bio-ph↗

DNA Segmentation as A Model Selection Process

Previous divide-and-conquer segmentation analyses of DNA sequences do not provide a satisfactory stopping criterion for the recursion. This paper proposes that segmentation be considered as a model selection process. Using the tools in model selection, a limit for the stopping criterion on the relaxed end can be determined. The Bayesian information criterion, in particular, provides a much more stringent stopping criterion than what is currently used. Such a stringent criterion can be used to delineate larger DNA domains. A relationship between the stopping criterion and the average domain size is empirically determined, which may aid in the determination of isochore borders.

physics.bio-ph↗

New stopping criteria for segmenting DNA sequences

We propose a solution on the stopping criterion in segmenting inhomogeneous DNA sequences with complex statistical patterns. This new stopping criterion is based on Bayesian Information Criterion (BIC) in the model selection framework. When this stopping criterion is applied to a left telomere sequence of yeast Saccharomyces cerevisiae and the complete genome sequence of bacterium Escherichia coli, borders of biologically meaningful units were identified (e.g. subtelomeric units, replication origin, and replication terminus), and a more reasonable number of domains was obtained. We also introduce a measure called segmentation strength which can be used to control the delineation of large domains. The relationship between the average domain size and the threshold of segmentation strength is determined for several genome sequences.

physics.bio-ph↗

A Complete Enumeration and Classification of Two-Locus Disease Models

There are 512 two-locus, two-allele, two-phenotype, fully-penetrant disease models. Using the permutation between two alleles, between two loci, and between being affected and unaffected, one model can be considered to be equivalent to another model under the corresponding permutation. These permutations greatly reduce the number of two-locus models in the analysis of complex diseases. This paper determines the number of non-redundant two-locus models (which can be 102, 100, 96, 51, 50, or 48, depending on which permutations are used, and depending on whether zero-locus and single-locus models are excluded). Whenever possible, these non-redundant two-locus models are classified by their property. Besides the familiar features of multiplicative models (logical AND), heterogeneity models (logical OR), and threshold models, new classifications are added or expanded: modifying-effect models, logical XOR models, interference and negative interference models (neither dominant nor recessive), conditionally dominant/recessive models, missing lethal genotype models, and highly symmetric models. The following aspects of two-locus models are studied: the marginal penetrance tables at both loci, the expected joint identity-by-descent probabilities, and the correlation between marginal identity-by-descent probabilities at the two loci. These studies are useful for linkage analyses using single-locus models while the underlying disease model is two-locus, and for correlation analyses using the linkage signals at different locations obtained by a single-locus model.

adap-org↗

The Study of Correlation Structures of DNA Sequences: A Critical Review

The study of correlation structure in the primary sequences of DNA is reviewed. The issues reviewed include: symmetries among 16 base-base correlation functions, accurate estimation of correlation measures, the relationship between $1/f$ and Lorentzian spectra, heterogeneity in DNA sequences, different modeling strategies of the correlation structure of DNA sequences, the difference of correlation structure between coding and non-coding regions (besides the period-3 pattern), and source of broad distribution of domain sizes. Although some of the results remain controversial, a body of work on this topic constitutes a good starting point for future studies.

adap-org↗

Understanding Long-range Correlations in DNA Sequences

In this paper, we review the literature on statistical long-range correlation in DNA sequences. We examine the current evidence for these correlations, and conclude that a mixture of many length scales (including some relatively long ones) in DNA sequences is responsible for the observed 1/f-like spectral component. We note the complexity of the correlation structure in DNA sequences. The observed complexity often makes it hard, or impossible, to decompose the sequence into a few statistically stationary regions. We suggest that, based on the complexity of DNA sequences, a fruitful approach to understand long-range correlation is to model duplication, and other rearrangement processes, in DNA sequences. One model, called ``expansion-modification system", contains only point duplication and point mutation. Though simplistic, this model is able to generate sequences with 1/f spectra. We emphasize the importance of DNA duplication in its contribution to the observed long-range correlation in DNA sequences.

chao-dyn↗