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Full-Text Articles in Computational Biology

Sample Size And Statistical Power Considerations In High-Dimensionality Data Settings: A Comparative Study Of Classification Algorithms, Yu Guo, Armin Garber, Raji Balasubramanian Sep 2010

Sample Size And Statistical Power Considerations In High-Dimensionality Data Settings: A Comparative Study Of Classification Algorithms, Yu Guo, Armin Garber, Raji Balasubramanian

Raji Balasubramanian

Background: Data generated using ‘omics’ technologies are characterized by high dimensionality, where the number of features measured per subject vastly exceeds the number of subjects in the study. In this paper, we consider issues relevant in the design of biomedical studies in which the goal is the discovery of a subset of features and an associated algorithm that can predict a binary outcome, such as disease status. We compare the performance of four commonly used classifiers (K-Nearest Neighbors, Prediction Analysis for Microarrays, Random Forests and Support Vector Machines) in high-dimensionality data settings. We evaluate the effects of varying levels of …


Wavelet-Based Functional Linear Mixed Models: An Application To Measurement Error–Corrected Distributed Lag Models, Elizabeth J. Malloy, Jeffrey S. Morris, Sara D. Adar, Helen Suh, Diane R. Gold, Brent A. Coull Jan 2010

Wavelet-Based Functional Linear Mixed Models: An Application To Measurement Error–Corrected Distributed Lag Models, Elizabeth J. Malloy, Jeffrey S. Morris, Sara D. Adar, Helen Suh, Diane R. Gold, Brent A. Coull

Jeffrey S. Morris

Frequently, exposure data are measured over time on a grid of discrete values that collectively define a functional observation. In many applications, researchers are interested in using these measurements as covariates to predict a scalar response in a regression setting, with interest focusing on the most biologically relevant time window of exposure. One example is in panel studies of the health effects of particulate matter (PM), where particle levels are measured over time. In such studies, there are many more values of the functional data than observations in the data set so that regularization of the corresponding functional regression coefficient …


Members’ Discoveries: Fatal Flaws In Cancer Research, Jeffrey S. Morris Jan 2010

Members’ Discoveries: Fatal Flaws In Cancer Research, Jeffrey S. Morris

Jeffrey S. Morris

A recent article published in The Annals of Applied Statistics (AOAS) by two MD Anderson researchers—Keith Baggerly and Kevin Coombes—dissects results from a highly-influential series of medical papers involving genomics-driven personalized cancer therapy, and outlines a series of simple yet fatal flaws that raises serious questions about the veracity of the original results. Having immediate and strong impact, this paper, along with related work, is providing the impetus for new standards of reproducibility in scientific research.


Statistical Contributions To Proteomic Research, Jeffrey S. Morris, Keith A. Baggerly, Howard B. Gutstein, Kevin R. Coombes Jan 2010

Statistical Contributions To Proteomic Research, Jeffrey S. Morris, Keith A. Baggerly, Howard B. Gutstein, Kevin R. Coombes

Jeffrey S. Morris

Proteomic profiling has the potential to impact the diagnosis, prognosis, and treatment of various diseases. A number of different proteomic technologies are available that allow us to look at many proteins at once, and all of them yield complex data that raise significant quantitative challenges. Inadequate attention to these quantitative issues can prevent these studies from achieving their desired goals, and can even lead to invalid results. In this chapter, we describe various ways the involvement of statisticians or other quantitative scientists in the study team can contribute to the success of proteomic research, and we outline some of the …


Informatics And Statistics For Analyzing 2-D Gel Electrophoresis Images, Andrew W. Dowsey, Jeffrey S. Morris, Howard G. Gutstein, Guang Z. Yang Jan 2010

Informatics And Statistics For Analyzing 2-D Gel Electrophoresis Images, Andrew W. Dowsey, Jeffrey S. Morris, Howard G. Gutstein, Guang Z. Yang

Jeffrey S. Morris

Whilst recent progress in ‘shotgun’ peptide separation by integrated liquid chromatography and mass spectrometry (LC/MS) has enabled its use as a sensitive analytical technique, proteome coverage and reproducibility is still limited and obtaining enough replicate runs for biomarker discovery is a challenge. For these reasons, recent research demonstrates the continuing need for protein separation by two-dimensional gel electrophoresis (2-DE). However, with traditional 2-DE informatics, the digitized images are reduced to symbolic data though spot detection and quantification before proteins are compared for differential expression by spot matching. Recently, a more robust and automated paradigm has emerged where gels are directly …


Bayesian Random Segmentationmodels To Identify Shared Copy Number Aberrations For Array Cgh Data, Veerabhadran Baladandayuthapani, Yuan Ji, Rajesh Talluri, Luis E. Nieto-Barajas, Jeffrey S. Morris Jan 2010

Bayesian Random Segmentationmodels To Identify Shared Copy Number Aberrations For Array Cgh Data, Veerabhadran Baladandayuthapani, Yuan Ji, Rajesh Talluri, Luis E. Nieto-Barajas, Jeffrey S. Morris

Jeffrey S. Morris

Array-based comparative genomic hybridization (aCGH) is a high-resolution high-throughput technique for studying the genetic basis of cancer. The resulting data consists of log fluorescence ratios as a function of the genomic DNA location and provides a cytogenetic representation of the relative DNA copy number variation. Analysis of such data typically involves estimation of the underlying copy number state at each location and segmenting regions of DNA with similar copy number states. Most current methods proceed by modeling a single sample/array at a time, and thus fail to borrow strength across multiple samples to infer shared regions of copy number aberrations. …


Quantitative Comparison Of Genomic-Wide Protein Domain Distributions, Arli A. Parikesit, Peter F. Stadler, Sonja J. Prohaska Jan 2010

Quantitative Comparison Of Genomic-Wide Protein Domain Distributions, Arli A. Parikesit, Peter F. Stadler, Sonja J. Prohaska

Arli A Parikesit

Investigations into the origins and evolution of regulatory mechanisms require quantitative estimates of the abundance and co-occurrence of functional protein domains among distantly related genomes. Currently available databases, such as the SUPERFAMILY, are not designed for quantitative comparisons since they are built upon transcript and protein annotations provided by the various different genome annotation projects. Large biases are introduced by the differences in genome annotation protocols, which strongly depend on the availability of transcript information and well-annotated closely related organisms. Here we show that the combination of de novo gene predictors and subsequent HMM-based annotation of SCOP domains in the …


Polyphyly Of The Pikeminnows (Teleostei: Cyprinidae) Inferred Using Mitochondrial Dna Sequences, T. Heath Ogden Dec 2009

Polyphyly Of The Pikeminnows (Teleostei: Cyprinidae) Inferred Using Mitochondrial Dna Sequences, T. Heath Ogden

T. Heath Ogden

The phylogenetic relationships of the Colorado pikeminnow Ptychocheilus lucius, northern pikeminnow P. oregonensis, Sacramento pikeminnow P. grandis, Umpqua pikeminnow P. umpquae, and hardhead Mylopharodon conocephalus were examined by using molecular data to investigate monophyly of the genus Ptychocheilus. Phylogenies generated using DNA sequence data from the cytochrome b and 16S ribosomal DNA genes of the mitochondrial genome reveal that Ptychocheilus is a polyphyletic genus and suggest that the taxonomy of the group is in need of further revision. These data yield insights into the evolution of the pikeminnows and help place the significant evolutionary events in context with the geological …