Computational Biology Commons^™

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards …

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 …

Prediction Of Lncrna-Disease Associations Based On Inductive Matrix Completion, Chengqian Lu, Mengyun Yang, Feng Luo, Fang-Xiang Wu, Min Li, Yi Pan, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. Mutations and dysregulations of lncRNAs are implicated in miscellaneous human diseases. Predicting lncRNA–disease associations is beneficial to disease diagnosis as well as treatment. Although many computational methods have been developed, precisely identifying lncRNA–disease associations, especially for novel lncRNAs, remains challenging.

Results: In this study, we propose a method (named SIMCLDA) for predicting potential lncRNA– disease associations based on inductive matrix completion. We compute Gaussian interaction profile kernel of lncRNAs from known lncRNA–disease interactions and functional similarity of diseases based on disease–gene and gene–gene onotology …

Development, Evaluation, And Application Of A Novel Error Correction Method For Next Generation Sequencing Data, Isaac Akogwu

Dissertations

Tremendous evolvement in sequencing technologies and the vast availability of data due to decreasing cost of Next-Generation-Sequencing (NGS) has availed scientists the opportunity to address a wide variety of evolutionary and biological issues. NGS uses massively parallel technology to accelerate the process at the expense of accuracy and read length in comparison to earlier Sanger methods. Therefore, computational limitations exist in how much analysis and information can be gleaned from the data without performing some form of error correction.

Error correction process is laborious and consumes a lot of computational resources. Despite the existence of many NGS data error correction …

P08. Unravelling Organelle Genome Evolution Architecture Using Rna-Sequencing Data, Matheus Sanita Lima, David Roy Smith

Western Research Forum

Background: Mitochondria genomes vary from 11 Mb to 6 kb, while plastids can vary from 1 Mb to 30 kb. Non-coding DNA accounts for most of this size variation, but the mechanistic and evolutionary reasons for that are still unknown. Next generation sequencing has generated unprecedented amounts of genomic and transcriptomic data that can be used for organelle genome evolution studies. However, most of these data is used only for the study of cell nucleus. Therefore, I decided to use these untapped data source to investigate the transcription of organelle genomes in plastid-bearing protists.

Methods: I mapped the transcriptomes over …

Annotation And Identification Of Several Glycerolipid Metabolic Related Ortholog Genes; Mrub_0437, Mrub_1813 And Mrub_2759 In The Organism Meithermus Ruber And Their Predicted Respective Orthologs B3926, B4042 And Bo514 Found In E.Coli., Abdul Rahman Abdul Kader, Dr. Lori R. Scott

Meiothermus ruber Genome Analysis Project

We predict Mrub_0437 encodes the enzyme glycerol kinase (DNA coordinates [417621..419183), which is an intermediary step of the glycerolipid metabolic pathway (KEGG map00561), It catalyzes the conversion of glycerol to sn-Glycerol-3-phosphate. The E. coli K12 MG1655 ortholog is predicted to be b3926.

We predict Mrub_1813 encodes the enzyme diacylglycerol kinase (DNA coordinates [1864659..1865063), which is an intermediary step of the glycerolipid metabolic pathway (KEGG map00561), It catalyzes the conversion of 1,2-diacyl-sn-glycerol to 1,2-diacyl-sn-glycerol 3-phosphate. The E. coli K12 MG1655 ortholog is predicted to be b4042.

We predict Mrub_2759 encodes the enzyme glycerol kinase (DNA coordinates [2799712..2800665), which is an intermediary …

Comparing An Atomic Model Or Structure To A Corresponding Cryo-Electron Microscopy Image At The Central Axis Of A Helix, Stephanie Zeil, Julio Kovacs, Willy Wriggers, Jing He

Computer Science Faculty Publications

Three-dimensional density maps of biological specimens from cryo-electron microscopy (cryo-EM) can be interpreted in the form of atomic models that are modeled into the density, or they can be compared to known atomic structures. When the central axis of a helix is detectable in a cryo-EM density map, it is possible to quantify the agreement between this central axis and a central axis calculated from the atomic model or structure. We propose a novel arc-length association method to compare the two axes reliably. This method was applied to 79 helices in simulated density maps and six case studies using cryo-EM …

Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots

STAR Program Research Presentations

The CRISPR-Cas system is an adaptive immune system found in bacteria which helps protect against the invasion of other microorganisms. This system induces double stranded breaks at precise genomic loci (1) in which repairs are initiated and insertions of a target are completed in the process. This mechanism can be used in eukaryotic cells in combination with sgRNAs (1) as a tool for genome editing. By using this CRISPR-Cas system, in addition to the “safe harbor locus,” ROSAβ26, the incorporation of a target gene into a site that is not susceptible to gene silencing effects can be achieved through few …

The Importance Of Physicochemical Characteristics And Nonlinear Classifiers In Determining Hiv-1 Protease Specificity, Timmy Manning, Paul Walsh

Department of Biological Sciences Publications

This paper reviews recent research relating to the application of bioinformatics approaches to determining HIV-1 protease specificity, outlines outstanding issues, and presents a new approach to addressing these issues. Leading machine learning theory for the problem currently suggests that the direct encoding of the physicochemical properties of the amino acid substrates is not required for optimal performance. A number of amino acid encoding approaches which incorporate potentially relevant physicochemical properties of the substrate are identified, and are evaluated using a nonlinear task decomposition based neuroevolution algorithm. The results are evaluated, and compared against a recent benchmark set on a nonlinear …

Characterization Of Putative Wnt3a-Inducible Enhancers, Katelynn C. Lee, Nicholas Hum, Aimy Sebastian, Gabriela Loots

STAR Program Research Presentations

The Wnt signaling pathway has been previously shown to play a major role in regulating bone metabolism and it is emerging as a target for the therapeutic intervention of bone thinning disorders such as osteoporosis. Several Wnt proteins have been shown to be expressed in bone and mutations in Wnt pathway members such as Wnt co-receptor Lrp5 and Wnt inhibitor Sost have been shown to be associated with low or high bone mass disorders, however, very little is known about specific roles played by different Wnt ligands in bone development, repair and remodeling. To identify downstream targets of Wnt signaling …

Functional Analysis Of Synthetic Gene Circuits Controlling A Protein Pump In Yeast, Junchen Diao

Dissertations and Theses (Open Access)

Synthetic biology aims to build biological devices to understand living systems and explore new applications. Synthetic gene circuits such as genetic switches, oscillators and logic gates are at the core of many synthetic biology applications. These gene circuits often include a sensor/regulator protein capable to detect small molecules and then transduce them into a regulatory signal to generate measurable output. Similar signal transduction networks are also abundant in nature. However, in many natural and engineered scenarios, the output also affects the regulator/sensor protein. How such interactions between the regulator/sensor and the output affect synthetic gene circuit function has not been …

Isquest: Finding Insertion Sequences In Prokaryotic Sequence Fragment Data, Abhishek Biswas, David T. Gauthier, Desh Ranjan, Mohammad Zubair

Computer Science Faculty Publications

Motivation: Insertion sequences (ISs) are transposable elements present in most bacterial and archaeal genomes that play an important role in genomic evolution. The increasing availability of sequenced prokaryotic genomes offers the opportunity to study ISs comprehensively, but development of efficient and accurate tools is required for discovery and annotation. Additionally, prokaryotic genomes are frequently deposited as incomplete, or draft stage because of the substantial cost and effort required to finish genome assembly projects. Development of methods to identify IS directly from raw sequence reads or draft genomes are therefore desirable. Software tools such as Optimized Annotation System for Insertion Sequences …

Linear Methods For Analysis And Quality Control Of Relative Expression Ratios From Quantitative Real-Time Polymerase Chain Reaction Experiments, Robert B. Page, Arnold J. Stromberg

Biology Faculty Publications

Relative expression quantitative real-time polymerase chain reaction (RT-qPCR) experiments are a common means of estimating transcript abundances across biological groups and experimental treatments. One of the most frequently used expression measures that results from such experiments is the relative expression ratio (R_E), which describes expression in experimental samples (i.e., RNA isolated from organisms, tissues, and/or cells that were exposed to one or more experimental or nonbaseline condition) in terms of fold change relative to calibrator samples (i.e., RNA isolated from organisms, tissues, and/or cells that were exposed to a control or baseline condition). Over the past decade, several …

Artificial Intelligence – Ii: Retinal Image Blood Vessel Segmentation, M. Usman Akram, Anam Tariq, Shoab A. Khan

International Conference on Information and Communication Technologies

The appearance and structure of blood vessels in retinal images play an important role in diagnosis of eye diseases. This paper proposes a method for segmentation of blood vessels in color retinal images. We present a method that uses 2-D Gabor wavelet to enhance the vascular pattern. We locate and segment the blood vessels using adaptive thresholding. The technique is tested on publicly available DRIVE database of manually labeled images which has been established to facilitate comparative studies on segmentation of blood vessels in retinal images. The proposed method achieves an area under the receiver operating characteristic curve of 0.963 …

Desulfovibrio Desulfuricans G20 Tetraheme Cytochrome Structure At 1.5 A˚ And Cytochrome Interaction With Metal Complexes, Mrunalini Pattarkine, J J. Tanner, C A. Bottoms, Y H. Lee, Judy D. Wall

Faculty Works

The structure of the type I tetraheme cytochrome c3 from Desulfovibrio desulfuricans G20 was determined to 1.5 A˚ by X-ray crystallography. In addition to the oxidized form, the structure of the molybdate-bound form of the protein was determined from oxidized crystals soaked in sodium molybdate. Only small structural shifts were obtained with metal binding, consistent with the remarkable structural stability of this protein. In vitro experiments with pure cytochrome showed that molybdate could oxidize the reduced cytochrome, although not as rapidly as U(VI) present as uranyl acetate. Alterations in the overall conformation and thermostability of the metal-oxidized protein were investigated …

Metaheuristic Applications And Their Solutions Quality, Dr. Zahid Hussain

International Conference on Information and Communication Technologies

Over the past few decades, a wide variety of classes of combinatorial problems (e.g. the assignment problem, the knapsack problem, the vehicle routing problem, etc.) have emerged - from such areas as management science, telecommunication, AI, VLSI design and many others. Many large combinatorial problems are NP-hard problems because of the combinatorial growth of their solution search space with the problem size. Such problems are commonly solved by some version of a prominent metaheuristic (e.g. Genetic Algorithms, Tabu Search, Simulated Annealing and etc.). These heuristics seek good but approximate solutions at a reasonable computational cost. These heuristics are of stochastic …

Computational Protein Biomarker Prediction: A Case Study For Prostate Cancer, Michael Wagner, Dayanand N. Naik, Alex Pothen, Srinivas Kasukurti, Raghu Ram Devineni, Bao-Ling Adam, O. John Semmes, George L. Wright Jr.

Mathematics & Statistics Faculty Publications

Background: Recent technological advances in mass spectrometry pose challenges in computational mathematics and statistics to process the mass spectral data into predictive models with clinical and biological significance. We discuss several classification-based approaches to finding protein biomarker candidates using protein profiles obtained via mass spectrometry, and we assess their statistical significance. Our overall goal is to implicate peaks that have a high likelihood of being biologically linked to a given disease state, and thus to narrow the search for biomarker candidates.

Results: Thorough cross-validation studies and randomization tests are performed on a prostate cancer dataset with over 300 patients, obtained …

Studies On The Formation Of Dna-Cationic Lipid Composite Films And Dna Hybridization In The Composites, Murali Sastry, Vidya Ramakrishnan, Mrunalini Pattarkine, Krishna N. Ganesh

Faculty Works

The formation of composite films of double-stranded DNA and cationic lipid molecules (octadecylamine, ODA) and the hybridization of complementary single-stranded DNA molecules in such composite films are demonstrated. The immobilization of DNA is accomplished by simple immersion of a thermally evaporated ODA film in the DNA solution at close to physiological pH. The entrapment of the DNA molecules in the cationic lipid film is dominated by attractive electrostatic interaction between the negatively charged phosphate backbone of the DNA molecules and the protonated amine molecules in the thermally evaporated film and has been quantified using quartz crystal microgravimetry (QCM). Fluorescence studies …

Cationic Surfactant Mediated Hybridization And Hydrophobization Of Dna Molecules At The Liquid/Liquid Interface And Their Phase Transfer, Murali Sastry, Ashavani Kumar, Mrunalini Pattarkine, Vidya Ramakrishnan, Krishna N. Ganesh

Faculty Works

Hybridization of complementary oligonucleotides mediated by a cationic surfactant at the water/hexane interface leads to hydrophobic, double-helical DNA which may be readily phase transferred to the organic phase and cast into thin films on solid substrates.

Hybridization Of Dna By Sequential Immobilization Of Oligonucleotides At The Air-Water Interface, Murali Sastry, Vidya Ramakrishnan, Mrunalini Pattarkine, Anand Gole, K. N. Ganesh

Faculty Works

The hybridization of DNA by sequential electrostatic and hydrogen-bonding immobilization of single-stranded complementary oligonucleotides at the air-water interface with cationic Langmuir monolayers is demonstrated. The complexation of the single-stranded DNA molecules with octadecylamine (ODA) Langmuir monolayers was followed in time by monitoring the pressure-area isotherms. A large (and slow) expansion of the ODA monolayer was observed during each stage of complexation in the following sequence: primary single-stranded DNA followed by complementary single-stranded DNA followed by the intercalator, ethidium bromide. Langmuir-Blodgett (LB) films of the ODA-DNA complex were formed on different substrates and characterized using quartz-crystal microgravimetry (QCM), Fourier transform infrared …

Anion Induced Blue To Purple Transition In Bacteriorhodopsin, Mrunalini Pattarkine, Anil K. Singh

Faculty Works

Purple membrane (PM, λ" role="presentation">λmax" role="presentation">max 570 nm) of H. halobium on treatment with sulphuric acid changes its colour to blue (λ" role="presentation">λmax" role="presentation">max 608 nm). The purple chromophore can be regenerated from the blue chromophore by exogeneous addition of anions such as CI−" role="presentation">− and HPO42−" role="presentation">2−4. Chloride ion is found to be more effective than the dibasic phosphate ion in regenerating the purple chromophore. Nevertheless, one thing common to the anion regeneration is that both CI−" role="presentation">− and HPO42−" role="presentation">2−4 show marked pH effect. At pH 1.0 the efficiency of …