Computational Biology Commons^™

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential …

Cophosk: A Method For Comprehensive Kinase Substrate Annotation Using Co-Phosphorylation Analysis, Marzieh Ayati, Danica D. Wiredja, Daniela M. Schlatzer, Sean Maxwell, Ming Li, Mehmet Koyutürk, Mark R. Chance

Faculty Scholarship

We present CoPhosK to predict kinase-substrate associations for phosphopeptide substrates detected by mass spectrometry (MS). The tool utilizes a Naïve Bayes framework with priors of known kinase-substrate associations (KSAs) to generate its predictions. Through the mining of MS data for the collective dynamic signatures of the kinases’ substrates revealed by correlation analysis of phosphopeptide intensity data, the tool infers KSAs in the data for the considerable body of substrates lacking such annotations. We benchmarked the tool against existing approaches for predicting KSAs that rely on static information (e.g. sequences, structures and interactions) using publically available MS data, including breast, colon, …

Mrub_3019 Casa Gene Is An Ortholog To E. Coli B2760, Kelsey Heiland, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This research is part of the Meiothermus ruber genome annotation project which aims to predict gene function with various bioinformatics tools. We investigated the function of Mrub_3019, which encodes the CasA protein involved in the multi-subunit effector complex for the CRISPR-Cas immunity system and predicted it to be an ortholog of E. coli K12 MG1655 b2760 (casA). We predicted that Mrub_3019 encodes the protein CasA, which is involved in PAM recognition of CRISPR interference pathway. Foreign DNA will bind to CasA, which signals Cas3 for helicase-mediated DNA degradation. Our hypothesis is supported by low E-values for pairwise alignment in NCBI …

Mrub_3015 Is Orthologous To The B2757 Gene Found In Escherichia Coli Coding For Casd, Ramona Collins, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of the gene Mrub_3015, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system. We predict that Mrub_3015 (DNA coordinates 3055550...3056245) encodes the the CRISPR-associated protein cas5, which is integral in maintaining the crRNA-DNA structure, keeping the complex from base pairing with the target phage DNA. Our hypothesis is supported by identical hits for Mrub_3015 and b2527 to the KEGG, Pfam, TIGRfam, CDD and PDB databases as well as a …

Mrub_3018 Is Orthologous To E. Coli B2759 (Casb), Kyle Parker, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We studied the biological activity of the Mrub_3018 gene, which we hypothesize is orthologous to E. coli gene B2759. We predicted that Mrub_3018(DNA coordinates 3057916… 3058524) encodes the protein CasB. CasB is a protein in the CRISPR CASCADE that will function as a structural protein. When the rest of the proteins form an “S” formation CasB will connect the front and back of the “S” creating a back bone for the structure. It will help bind DNA …

Iris-Eda: An Integrated Rna-Seq Interpretation System For Gene Expression Data Analysis, Brandon Monier, Adam Mcdermaid, Cankun Wang, Jing Zhao, Allison Miller, Anne Fennell, Qin Ma

Agronomy, Horticulture and Plant Science Faculty Publications

Next-Generation Sequencing has made available substantial amounts of large-scale Omics data, providing unprecedented opportunities to understand complex biological systems. Specifically, the value of RNA-Sequencing (RNA-Seq) data has been confirmed in inferring how gene regulatory systems will respond under various conditions (bulk data) or cell types (single-cell data). RNA-Seq can generate genome-scale gene expression profiles that can be further analyzed using correlation analysis, co-expression analysis, clustering, differential gene expression (DGE), among many other studies. While these analyses can provide invaluable information related to gene expression, integration and interpretation of the results can prove challenging. Here we present a tool called IRIS-EDA, …

Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon

Theses and Dissertations

This study phylogenetically analyzed 30 AMY-related genes from 11 primates. The results show the gradual expansion of the AMY gene family which could have allowed primates to adapt to various ecological landscapes and maximize energy intake from starch-rich foods in periods of food scarcity.

A Novel Pathway-Based Distance Score Enhances Assessment Of Disease Heterogeneity In Gene Expression, Yunqing Liu, Xiting Yan

Yale Day of Data

Distance-based unsupervised clustering of gene expression data is commonly used to identify heterogeneity in biologic samples. However, high noise levels in gene expression data and the relatively high correlation between genes are often encountered, so traditional distances such as Euclidean distance may not be effective at discriminating the biological differences between samples. In this study, we developed a novel computational method to assess the biological differences based on pathways by assuming that ontologically defined biological pathways in biologically similar samples have similar behavior. Application of this distance score results in more accurate, robust, and biologically meaningful clustering results in both …

Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing, Taylor Adams, Jonas Schupp

Yale Day of Data

This poster illustrates the differences between the IPF disease-specific variety of lung macrophages and the two varieties of macrophages known to reside in the normal human lung.

Cyclin C: The Story Of A Non-Cycling Cyclin, Jan Jezek, Daniel G J Smethurst, David C Stieg, Z A C Kiss, Sara E Hanley, Vidyaramanan Ganesan, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit …

Mrub_3014 Is Orthologous To B2756, Samir Abdelkarim, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of the gene Mrub_3014, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system. We predict that Mrub_3014 (DNA coordinates 3054943..3055575) encodes CRISPR-associated protein Cse3/case which function as an endonuclease. Our hypothesis is supported by identical hits for Mrub_3014 and b2756 to the KEGG, Pfam, TIGRfam, CDD and PDB databases, as well as a low E-value for a pairwise NCBI BLAST comparison. Both protein products are predicted to be localized …

M. Ruber Mrub_3013 Is Orthologous To E. Coli B2755, Laura Butcher, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of gene Mrub_3013, which we hypothesize is orthologous to b2755 in E. coli K12 MG1655 (a.k.a. Cas1). We investigated the biological function of a gene with the M. ruber locus tag of Mrub_3013, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system in M. ruber. We predict that Mrub_3013 (DNA coordinates 3,053,978-3,054,940) encodes the protein Cas1 which as part of the CRISPR-Cas system, selects and cuts the foreign …

Mrub_3020, A Paralog Of Mrub_1489, Is Orthologous To E. Coli Casc (Locus Tag B2761), Alfred Dei-Ampeh, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological functions of two genes: mrub_3020 and mrub_1489. We make two hypotheses in this investigation: a) mrub_3020 is orthologous to the gene b2761 in E. coli K12 MG1655 (a.k.a. casC); b) mrub_1489 is a paralog of mrub_3020. We also predict that the two genes encode unique proteins: mrub_3020 with DNA coordinates 3060491…3063190 encodes a CRISPR – associated helicase (Cas3) that supports the Cascade complex of the CRISPR – Cas adaptive immune system …

Transcription Factor Binding Site Clusters Identify Target Genes With Similar Tissue-Wide Expression And Buffer Against Mutations., Peter Rogan, Ruipeng Lu

Biochemistry Publications

Background: The distribution and composition of cis-regulatory modules composed of transcription factor (TF) binding site (TFBS) clusters in promoters substantially determine gene expression patterns and TF targets. TF knockdown experiments have revealed that TF binding profiles and gene expression levels are correlated. We use TFBS features within accessible promoter intervals to predict genes with similar tissue-wide expression patterns and TF targets using Machine Learning (ML). Methods: Bray-Curtis Similarity was used to identify genes with correlated expression patterns across 53 tissues. TF targets from knockdown experiments were also analyzed by this approach to set up the ML framework. TFBSs were …

Overview Of Direct Thrombin Inhibitors For Use In Staphylococcus Aereus Infections, Joseph C. Risler

Honors Undergraduate Theses

The pathogenicity and intractable nature of the microorganism Staphylococcus aureus (SA) has been long documented and highlighted by many health care agencies, with emphasis on its ability to exploit the human coagulation system to deadly effect. Two drugs from a class of inhibitors known as Direct Thrombin Inhibitors (DTI) have been shown to have a substantial effect on the enzyme secreted by SA known as Staphylocoagulase (SC), but up until now the application of this potential treatment has been limited. This paper strives to supply an overview of these clinical studies and propose a novel protocol for testing DTI's on …

Contemporary Sexual Selection Does Not Explain Variation In Male Display Traits Among Populations, J. Colton Watts, Allissa Flynn, Brigitte Tenhumberg, Eileen Hebets

Brigitte Tenhumberg Papers

Sexual selection is widely hypothesized to facilitate the evolution of reproductive isolation through divergence in sexual traits and sexual trait preferences among populations. However, direct evidence of divergent sexual selection causing intraspecific trait divergence remains limited. Using the wolf spider Schizocosa crassipes, we characterized patterns of female mate choice within and among geographic locations and related those patterns to geographic variation in male display traits to test whether divergent sexual selection caused by mate choice explains intraspecific trait variation. We found evidence of phenotypic selection on male behavior arising from female mate choice, but no evidence that selection varied …

Association Genetics And Local Adaptation Of Populus Trichocarpa Torr. & Gray, Hari Bahadur Chhetri

Graduate Theses, Dissertations, and Problem Reports (ETD)

A major goal in plant science is overcoming the recalcitrance of plant biomass to cellulose extraction, to enable efficient production of cellulosic biofuel. We have started to understand the genetic basis of some important traits such as cell wall chemistry, but we do not know anything about the key structural and functional traits such as wood anatomy that greatly affect plant biomass recalcitrance. Furthermore, biofuel feedstocks have to be adapted to varied environmental conditions to ensure high productivity in plantations, but little is known about the molecular mechanisms underlying local adaptation. With the advancement in sequencing and genotyping technologies, association …

Intraspecific Variation In Dehydration Tolerance: Insights From The Tropical Plant Marchantia Inflexa, Rose A. Marks

Theses and Dissertations--Biology

Plants are threatened by global change, increasing variability in weather patterns, and associated abiotic stress. Consequently, there is an urgent need to enhance our ability to predict plant community dynamics, shifts in species distributions, and physiological responses to environmental challenges. By building a fundamental understanding of plant stress tolerance, it may be possibly to protect the ecological services, economic industries, and communities that depend on plants. Dehydration tolerance (DhT) is an important mechanism of water stress tolerance with promising translational applications. Here, I take advantage natural variation in DhT to gain a deeper insight into this complex trait. In addition, …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

A Comparative Evaluation Of The Generalised Predictive Ability Of Eight Machine Learning Algorithms Across Ten Clinical Metabolomics Data Sets For Binary Classification, Kevin M. Mendez, Stacey N. Reinke, David I. Broadhurst

Research outputs 2014 to 2021

Introduction:

Metabolomics is increasingly being used in the clinical setting for disease diagnosis, prognosis and risk prediction. Machine learning algorithms are particularly important in the construction of multivariate metabolite prediction. Historically, partial least squares (PLS) regression has been the gold standard for binary classification. Nonlinear machine learning methods such as random forests (RF), kernel support vector machines (SVM) and artificial neural networks (ANN) may be more suited to modelling possible nonlinear metabolite covariance, and thus provide better predictive models.

Objectives:

We hypothesise that for binary classification using metabolomics data, non-linear machine learning methods will provide superior generalised predictive ability when …