Life Sciences Commons^™

Causal Inference In Hybrid Intervention Trials Involving Treatment Choice, Qi Long, Rod Little, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Comparison Of Methods For Estimating The Causal Effect Of A Treatment In Randomized Clinical Trials Subject To Noncompliance, Rod Little, Qi Long, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Group Additive Regression Models For Genomic Data Analysis, Yihui Luan, Hongzhe Li

UPenn Biostatistics Working Papers

One important problem in genomic research is to identify genomic features such as gene expression data or DNA single nucleotide polymorphisms (SNPs) that are related to clinical phenotypes. Often these genomic data can be naturally divided into biologically meaningful groups such as genes belonging to the same pathways or SNPs within genes. In this paper, we propose group additive regression models and a group gradient descent boosting procedure for identifying groups of genomic features that are related to clinical phenotypes. Our simulation results show that by dividing the variables into appropriate groups, we can obtain better identification of the group …

Extensions To Gene Set Enrichment, Zhen Jiang, Robert Gentleman

Bioconductor Project Working Papers

Motivation: Gene Set Enrichment Analysis (GSEA) has been developed recently to capture moderate but coordinated changes in the expression of sets of functionally related genes. We propose number of extensions to GSEA, which uses different statistics to describe the association between genes and phenotype of interest. We make use of dimension reduction procedures, such as principle component analysis to identify gene sets containing coordinated genes. We also address the problem of overlapping among gene sets in this paper.

Results: We applied our methods to the data come from a clinical trial in acute lymphoblastic leukemia (ALL) [1]. We identified interesting …

Fdr And Bayesian Multiple Comparisons Rules, Peter Muller, Giovanni Parmigiani, Kenneth Rice

Johns Hopkins University, Dept. of Biostatistics Working Papers

We discuss Bayesian approaches to multiple comparison problems, using a decision theoretic perspective to critically compare competing approaches. We set up decision problems that lead to the use of FDR-based rules and generalizations. Alternative definitions of the probability model and the utility function lead to different rules and problem-specific adjustments. Using a loss function that controls realized FDR we derive an optimal Bayes rule that is a variation of the Benjamini and Hochberg (1995) procedure. The cutoff is based on increments in ordered posterior probabilities instead of ordered p- values. Throughout the discussion we take a Bayesian perspective. In particular, …

Exploration, Normalization, And Genotype Calls Of High Density Oligonucleotide Snp Array Data, Benilton Carvalho, Terence P. Speed, Rafael A. Irizarry

Johns Hopkins University, Dept. of Biostatistics Working Papers

In most microarray technologies, a number of critical steps are required to convert raw intensity measurements into the data relied upon by data analysts, biologists and clinicians. These data manipulations, referred to as preprocessing, can influence the quality of the ultimate measurements. In the last few years, the high-throughput measurement of gene expression is the most popular application of microarray technology. For this application, various groups have demonstrated that the use of modern statistical methodology can substantially improve accuracy and precision of gene expression measurements, relative to ad-hoc procedures introduced by designers and manufacturers of the technology. Currently, other applications …

Optimal Adaptation Of Web Processes With Inter-Service Dependencies, Kunal Verma, Prashant Doshi, Karthik Gomadam, John A. Miller, Amit P. Sheth

Kno.e.sis Publications

We present methods for optimally adapting Web processes to exogenous events while preserving inter-service dependencies. For example, in a supply chain process, orders placed by the manufacturer may get delayed in arriving. In response to this event, the manufacturer has the choice of either waiting out the delay or changing the supplier. Additionally, there may be compatibility constraints between the different orders, thereby introducing the problem of coordination between them if the manufacturer chooses to change the suppliers. We present our methods within the framework of autonomic Web processes. This framework seeks to add properties of self-configuration, adaptation, and self-optimization …

Querying Formal Contexts With Answer Set Programs, Pascal Hitzler, Markus Krotzsch

Computer Science and Engineering Faculty Publications

Recent studies showed how a seamless integration of formal concept analysis (FCA), logic of domains, and answer set programming (ASP) can be achieved. Based on these results for combining hierarchical knowledge with classical rule-based formalisms, we introduce an expressive common-sense query language for formal contexts. Although this approach is conceptually based on order-theoretic paradigms, we show how it can be implemented on top of standard ASP systems. Advanced features, such as default negation and disjunctive rules, thus become practically available for processing contextual data.

Geospatial Ontology Development And Semantic Analytics, I. Budak Arpinar, Cartic Ramakrishnan, Molly Azami, Amit P. Sheth, E. Lynn Usery, Mei-Po Kwan

Kno.e.sis Publications

Geospatial ontology development and semantic knowledge discovery addresses the need for modeling, analyzing and visualizing multimodal information, and is unique in offering integrated analytics that encompasses spatial, temporal and thematic dimensions of information and knowledge. The comprehensive ability to provide integrated analysis from multiple forms of information and use of explicit knowledge make this approach unique. This also involves specification of spatiotemporal thematic ontologies and populating such ontologies with high quality knowledge. Such ontologies form the basis for defining the meaning of important relations terms, such as near or surrounded by, and enable computation of spatiotemporal thematic proximity measures we …

Multivariate Analysis And Visualization Of Splicing Correlations In Single-Gene Transcriptomes, Mark C. Emerick, Giovanni Parmigiani, William S. Agnew

Johns Hopkins University, Dept. of Biostatistics Working Papers

Through ‘combinatorial splicing’, RNA metabolism may create enormous structural diversity in the proteome. Functional interactions among multiple alternative domains can have a disproportionate impact on the phenotype, requiring integrated RNA-level regulation of molecular composition. Splicing correlations within molecules expressed from a single gene, where these effects would be greatest, provide valuable clues to functional relationships and targets for splicing regulation. We present tools to visualize complex splicing patterns in full-length cDNA libraries. Developmental changes in pair-wise correlations are presented vectorially in ‘clock plots’ and linkage grids. Higher-order correlations are assessed via a loglinear model and Monte Carlo analysis with an …

Bi-Level Clustering Of Mixed Categorical And Numerical Biomedical Data, Bill Andreopoulos, Aijun An, Xiaogang Wang

Faculty Publications, Computer Science

Biomedical data sets often have mixed categorical and numerical types, where the former represent semantic information on the objects and the latter represent experimental results. We present the BILCOM algorithm for |Bi-Level Clustering of Mixed categorical and numerical data types|. BILCOM performs a pseudo-Bayesian process, where the prior is categorical clustering. BILCOM partitions biomedical data sets of mixed types, such as hepatitis, thyroid disease and yeast gene expression data with Gene Ontology annotations, more accurately than if using one type alone.

Plasq: A Generalized Linear Model-Based Procedure To Determine Allelic Dosage Ini Cancer Cells From Snp Array Data, Thomas Laframboise, David P. Harrington, Barbara A. Weir

Harvard University Biostatistics Working Paper Series

No abstract provided.

Masquerader Detection Using Oclep: One-Class Classification Using Length Statistics Of Emerging Patterns, Lijun Chen, Guozhu Dong

Kno.e.sis Publications

We introduce a new method for masquerader detection that only uses a user’s own data for training, called Oneclass Classification using Length statistics of Emerging Patterns (OCLEP). Emerging patterns (EPs) are patterns whose support increases from one dataset/class to another with a big ratio, and have been very useful in earlier studies. OCLEP classifies a case T as self or masquerader by using the average length of EPs obtained by contrasting T against sets of samples of a user’s normal data. It is based on the observation that one needs long EPs to differentiate instances from a common class, but …

A Metamodel And Uml Profile For Rule-Extended Owl Dl Ontologies, Saartje Brockmans, Peter Haase, Pascal Hitzler, Rudi Studer

Computer Science and Engineering Faculty Publications

In this paper we present a MOF compliant metamodel and UML profile for the Semantic Web Rule Language (SWRL) that integrates with our previous work on a metamodel and UML profile for OWL DL. Based on this metamodel and profile, UML tools can be used for visual modeling of rule-extended ontologies.

Semantic Empowerment Of Health Care And Life Science Applications, Amit P. Sheth

Kno.e.sis Publications

No abstract provided.

Bounded Search For De Novo Identification Of Degenerate Cis-Regulatory Elements, Jonathan M. Carlson, Arijit Chakravarty, Radhika S. Khetani, Robert H. Gross

Dartmouth Scholarship

The identification of statistically overrepresented sequences in the upstream regions of coregulated genes should theoretically permit the identification of potential cis-regulatory elements. However, in practice many cis-regulatory elements are highly degenerate, precluding the use of an exhaustive word-counting strategy for their identification. While numerous methods exist for inferring base distributions using a position weight matrix, recent studies suggest that the independence assumptions inherent in the model, as well as the inability to reach a global optimum, limit this approach.

In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng

Honors Scholar Theses

The major histocompatibility complex (MHC) is a gene family responsible for many critical functions of the immune system in most vertebrates. The MHC consists of three classes differentiated by their structure and function, and MHC class I encodes antigen binding proteins as well as chaperone and accessory proteins such as tapasin. The purpose of this project is to reconstitute several human MHC class I molecules in their peptide-filled and peptide-deficient forms, and to purify these proteins for biochemical study. The expressed proteins include wild type and mutant variants of the fusion protein human leukocyte antigen HLA-B*0801-fos, and human beta-2-microglobulin (β2m). …

Narrowed Tcr Repertoire And Viral Escape As A Consequence Of Heterologous Immunity, Markus Cornberg, Alex T. Chen, Lee A. Wilkinson, Michael A. Brehm, Sung-Kwon Kim, Claudia Calcagno, Dario Ghersi, Roberto Puzone, Franco Celada, Raymond M. Welsh, Liisa K. Selin

Interdisciplinary Informatics Faculty Publications

Why some virus-specific CD8 TCR repertoires are diverse and others restricted or “oligoclonal” has been unknown. We show here that oligoclonality and extreme clonal dominance can be a consequence ofTcell crossreactivity. Lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PV) encode NP205–212 epitopes that induce different but highly cross-reactive diverseTCRrepertoires. Homologous viral challenge ofimmune mice only slightly skewed the repertoire and enriched for predictable TCR motifs. However, heterologous viral challenge resulted in a narrow oligoclonal repertoire with dominant clones with unpredictableTCRsequences.This shift in clonal dominance varied with the private, i.e., unique, specificity of the host’s TCR repertoire and was simulated using …

Semantic Analytics Visualization, Leonidas Deligiannidis, Amit P. Sheth, Boanerges Aleman-Meza

Kno.e.sis Publications

In this paper we present a new tool for semantic analytics through 3D visualization called “Semantic Analytics Visualization” (SAV). It has the capability for visualizing ontologies and meta-data including annotated web-documents, images, and digital media such as audio and video clips in a synthetic three-dimensional semi-immersive environment. More importantly, SAV supports visual semantic analytics, whereby an analyst can interactively investigate complex relationships between heterogeneous information. The tool is built using Virtual Reality technology which makes SAV a highly interactive system. The backend of SAV consists of a Semantic Analytics system that supports query processing and semantic association discovery. Using a …

Psd-Project Sequence Database, Matthew Kayala, Akhila Kambhampati, Stephanie Forschner, Bethany D. Jenkins

Bioinformatics Software Design Projects

1. Introduction

The sequencing of nucleic acids and the subsequent analysis of their encoded the genes and proteins has revolutionized biological sciences and allowed for the determination of evolutionary origins and biochemical potential of organisms. While the technology to determine molecular sequence data has become extremely powerful in terms of both automation and thoughput, sequence analysis technology has lagged behind, unable to efficiently keep up with the vast amount of sequence data being generated both in individual labs and by researchers worldwide. The foundation of robust sequence analysis is dependent on the building and maintaining of project sequence databases (PSD) …

Accuracy And Self Correction Of Information Received From An Internet Breast Cancer List: Content Analysis, Adol Esquivel, Funda Meric-Bernstam, Elmer V Bernstam

Faculty, Staff and Student Publications

OBJECTIVES: To determine the prevalence of false or misleading statements in messages posted by internet cancer support groups and whether these statements were identified as false or misleading and corrected by other participants in subsequent postings. DESIGN: Analysis of content of postings. SETTING: Internet cancer support group Breast Cancer Mailing List. MAIN OUTCOME MEASURES: Number of false or misleading statements posted from 1 January to 23 April 2005 and whether these were identified and corrected by participants in subsequent postings. RESULTS: 10 of 4600 postings (0.22%) were found to be false or misleading. Of these, seven were identified as false …

Method Of Predicting Splice Sites Based On Signal Interactions, Alexander Churbanov, Igor B. Rogozin, Jitender S. Deogun, Hesham Ali

Information Systems and Quantitative Analysis Faculty Publications

Background: Predicting and proper ranking of canonical splice sites (SSs) is a challenging problem in bioinformatics and machine learning communities. Any progress in SSs recognition will lead to better understanding of splicing mechanism. We introduce several new approaches of combining a priori knowledge for improved SS detection. First, we design our new Bayesian SS sensor based on oligonucleotide counting. To further enhance prediction quality, we applied our new de novo motif detection tool MHMMotif to intronic ends and exons. We combine elements found with sensor information using Naive Bayesian Network, as implemented in our new tool SpliceScan.

Results: …

Selecting 'Significant' Differentially Expressed Genes From The Combined Perspective Of The Null And The Alternative, Beatrijs Moerkerke, Els Goetghebeur

Harvard University Biostatistics Working Paper Series

No abstract provided.

Ivibrate: Interactive Visualization Based Framework For Clustering Large Datasets, Keke Chen, Ling Liu

Kno.e.sis Publications

With continued advances in communication network technology and sensing technology, there is astounding growth in the amount of data produced and made available through cyberspace. Efficient and high-quality clustering of large datasets continues to be one of the most important problems in large-scale data analysis. A commonly used methodology for cluster analysis on large datasets is the three-phase framework of sampling/summarization, iterative cluster analysis, and disk-labeling. There are three known problems with this framework which demand effective solutions. The first problem is how to effectively define and validate irregularly shaped clusters, especially in large datasets. Automated algorithms and statistical methods …

Detecting The Change Of Clustering Structure In Categorical Data Streams, Keke Chen, Ling Liu

Kno.e.sis Publications

Analyzing clustering structures in data streams can provide critical information for making decision in real time. In this paper, we present a framework for detecting the change of critical clustering structure in categorical data streams. The framework consists of the Hierarchical Entropy Tree structure (HE-Tree) and the extended ACE clustering algorithm. HE-Tree can efficiently capture the entropy property of the categorical data streams and allow us to draw precise clustering information from the data stream for high-quality BkPLots with the extended ACE algorithm.

Semantic Web Applications In Financial Industry, Government, Health Care And Life Sciences, Amit P. Sheth

Kno.e.sis Publications

No abstract provided.

Feature-Level Exploration Of The Choe Et Al. Affymetrix Genechip Control Dataset, Rafael A. Irizarry, Leslie Cope, Zhijin Wu

Johns Hopkins University, Dept. of Biostatistics Working Papers

We describe why the Choe et al. control dataset should not be used to assess GeneChip expression measures.

Genome Scanning Methods For Comparing Sequences Between Groups, With Application To Hiv Vaccine Trials, Peter B. Gilbert, Chunyuan Wu, David V. Jobes

UW Biostatistics Working Paper Series

Consider a placebo-controlled preventive HIV vaccine efficacy trial. An HIV amino acid sequence is measured from each volunteer who acquires HIV, and these sequences are aligned together with the reference HIV sequence represented in the vaccine. We develop genome scanning methods to identify HIV positions at which the amino acids in sequences from infected vaccine recipients tend to be more divergent from the corresponding reference amino acid than the amino acids in sequences from infected placebo recipients. We consider five two-sample test statistics, based on Euclidean, Mahalanobis, and Kullback-Leibler divergence measures. Weights are incorporated to reflect biological information contained in …

2^K Factorials In Blocks Of Size 2, With Application To Two-Color Microarray Experiments, Kathleen F. Kerr

UW Biostatistics Working Paper Series

When a two-level design must be run in blocks of size two, there is a unique blocking scheme that enables estimation of all the main effects. Unfortunately this design does not enable estimation of any two-factor interactions. When the experimental goal is to estimate all main effects and two-factor interactions, it is necessary to combine replicates of the experiment that use different blocking schemes. In this paper we identify such designs for up to eight factors that enable estimation of all main effects and two-factor interactions with the fewest number of replications. In addition, we give a construction for general …

Wsdl-S: Specification, Tools, Use Cases And Applications, Amit P. Sheth, Kunal Verma, Karthik Gomadam

Kno.e.sis Publications

No abstract provided.