Bioinformatics Commons^™

Visualization And Interpretation Of Protein Interactions, Dipanjan Chatterjee

Electronic Thesis and Dissertation Repository

Visualization and interpretation of deep learning models' prediction is a very important area of research in machine learning nowadays. Researchers are not only focused on generating a model with good performance, but also they want to trust the model. Our aim in this thesis is to adapt existing interpretation methods to a protein-protein binding site prediction problem to visualize and understand the model's prediction and learning pattern.

We present three deep learning-based interpretation methods: sensitivity analysis, saliency map and integrated gradients to analyze the amino acid residues which create positive and negative relevance to the deep learning models' prediction. As …

Analysis Of Motif Distributions In Regions Of Endocytic Proteins, Chante Bethell, Stephanie J. Spielman, Phd

STEM Student Research Symposium Posters

A short linear motif (SLiM) is a recurring pattern of approximately three to ten amino acids found in proteins. SLiMs are important for cellular signaling and the regulating of proteins, often times by acting as binding sites for protein-binding domains. While SLiMs exist both in ordered regions of proteins where there is a tertiary structure and in disordered regions where there is no structure, they are primarily functional in disordered regions. An important example of SLiM-mediated processes and the focus of this study is endocytosis. Endocytosis is the process by which cells engulf molecules from the extracellular environment. There are …

New Methods To Improve Protein Structure Modeling, Maha Abdelrasoul

Computer Science Theses & Dissertations

Proteins are considered the central compound necessary for life, as they play a crucial role in governing several life processes by performing the most essential biological and chemical functions in every living cell. Understanding protein structures and functions will lead to a significant advance in life science and biology. Such knowledge is vital for various fields such as drug development and synthetic biofuels production.

Most proteins have definite shapes that they fold into, which are the most stable state they can adopt. Due to the fact that the protein structure information provides important insight into its functions, many research efforts …

The Dissemination, Regulatory Role, And Evolution Of Mycobacterial Inteins, Danielle Skye Kelley

Legacy Theses & Dissertations (2009 - 2024)

Inteins are intervening protein elements, capable of coordinating escape from a host protein through a self-catalyzed mechanism, called protein splicing. This results in free intein and a mature host protein product. Inteins are also mobile elements and many contain homing endonucleases that enable the targeting to ectopic sites and invasion of novel niches. Inteins have been found across all three domains of life and are often present in replication, recombination, and repair proteins. However, it is unclear if the observed distribution is simply a factor of endonuclease preference or if inteins have been selectively maintained due to an adaptation that …

In Search Of A Function For An Uncharacterized Conserved Protein In Streptococcus Sanguinis Sk36, Ayana Scott-Elliston

Theses and Dissertations

With the number of fully sequenced bacterial genomes increasing in the past 7 years, it has been discovered that a large percentage of the putative protein coding genes have no known function. This lack of knowledge leaves scientists with an incomplete understanding of bacteria. In this study, conserved hypothetical protein mutants from Streptococcus sanguinis SK36 were screened on solid media with various environmental conditions. From these screens, the candidate protein, SSA_2372, displayed a sensitivity to acidic conditions. Its homolog in Bacillus subtilis 168, BSU00030, also displayed a sensitivity to pH conditions at its acid tolerance extremes unlike its other homolog …

Interactomics-Based Functional Analysis: Using Interaction Conservation To Probe Bacterial Protein Functions, J. Harry Caufield

Theses and Dissertations

The emergence of genomics as a discrete field of biology has changed humanity’s understanding of our relationship with bacteria. Sequencing the genome of each newly-discovered bacterial species can reveal novel gene sequences, though the genome may contain genes coding for hundreds or thousands of proteins of unknown function (PUFs). In some cases, these coding sequences appear to be conserved across nearly all bacteria. Exploring the functional roles of these cases ideally requires an integrative, cross-species approach involving not only gene sequences but knowledge of interactions among their products. Protein interactions, studied at genome scale, extend genomics into the field of …

Computational Development For Secondary Structure Detection From Three-Dimensional Images Of Cryo-Electron Microscopy, Dong Si

Computer Science Theses & Dissertations

Electron cryo-microscopy (cryo-EM) as a cutting edge technology has carved a niche for itself in the study of large-scale protein complex. Although the protein backbone of complexes cannot be derived directly from the medium resolution (5-10 Å) of amino acids from three-dimensional (3D) density images, secondary structure elements (SSEs) such as alpha-helices and beta-sheets can still be detected. The accuracy of SSE detection from the volumetric protein density images is critical for ab initio backbone structure derivation in cryo-EM. So far it is challenging to detect the SSEs automatically and accurately from the density images at these resolutions. This dissertation …

Beta Atomic Contacts: Identifying Critical Specific Contacts In Protein Binding Interfaces, Qian Lu, Chee Keong Kwoh, Steven C. H. Hoi

Research Collection School Of Computing and Information Systems

Specific binding between proteins plays a crucial role in molecular functions and biological processes. Protein binding interfaces and their atomic contacts are typically defined by simple criteria, such as distance-based definitions that only use some threshold of spatial distance in previous studies. These definitions neglect the nearby atomic organization of contact atoms, and thus detect predominant contacts which are interrupted by other atoms. It is questionable whether such kinds of interrupted contacts are as important as other contacts in protein binding. To tackle this challenge, we propose a new definition called beta (β) atomic contacts. Our definition, founded on the …

Utilizing Nmr Spectroscopy And Molecular Docking As Tools For The Structural Determination And Functional Annotation Of Proteins, Jaime Stark

Department of Chemistry: Dissertations, Theses, and Student Research

With the completion of the Human Genome Project in 2001 and the subsequent explosion of organisms with sequenced genomes, we are now aware of nearly 28 million proteins. Determining the role of each of these proteins is essential to our understanding of biology and the development of medical advances. Unfortunately, the experimental approaches to determine protein function are too slow to investigate every protein. Bioinformatics approaches, such as sequence and structure homology, have helped to annotate the functions of many similar proteins. However, despite these computational approaches, approximately 40% of proteins still have no known function. Alleviating this deficit will …

Planning Combinatorial Disulfide Cross-Links For Protein Fold Determination, Fei Xiong, Alan M Friedman, Chris Bailey-Kellogg

Dartmouth Scholarship

Fold recognition techniques take advantage of the limited number of overall structural organizations, and have become increasingly effective at identifying the fold of a given target sequence. However, in the absence of sufficient sequence identity, it remains difficult for fold recognition methods to always select the correct model. While a native-like model is often among a pool of highly ranked models, it is not necessarily the highest-ranked one, and the model rankings depend sensitively on the scoring function used. Structure elucidation methods can then be employed to decide among the models based on relatively rapid biochemical/biophysical experiments.

A Comparison Of The Functional Modules Identified From Time Course And Static Ppi Network Data, Xiwei Tang, Jianxin Wang, Binbin Liu, Min Li, Gang Chen, Yi Pan

Computer Science Faculty Publications

Background: Cellular systems are highly dynamic and responsive to cues from the environment. Cellular function and response patterns to external stimuli are regulated by biological networks. A protein-protein interaction (PPI) network with static connectivity is dynamic in the sense that the nodes implement so-called functional activities that evolve in time. The shift from static to dynamic network analysis is essential for further understanding of molecular systems.

Results: In this paper, Time Course Protein Interaction Networks (TC- PINs) are reconstructed by incorporating time series gene expression into PPI networks. Then, a clustering algorithm is used to create functional modules from three …

Optimization Algorithms For Functional Deimmunization Of Therapeutic Proteins, Andrew S. Parker, Wei Zheng, Karl E. Griswold, Chris Bailey-Kellogg

Dartmouth Scholarship

To develop protein therapeutics from exogenous sources, it is necessary to mitigate the risks of eliciting an anti-biotherapeutic immune response. A key aspect of the response is the recognition and surface display by antigen-presenting cells of epitopes, short peptide fragments derived from the foreign protein. Thus, developing minimal-epitope variants represents a powerful approach to deimmunizing protein therapeutics. Critically, mutations selected to reduce immunogenicity must not interfere with the protein's therapeutic activity.

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.

A Novel Approach To Phylogenetic Tree Construction Using Stochastic Optimization And Clustering, Ling Qin, Yixin Chen, Yi Pan, Ling Chen

Computer Science Faculty Publications

Background: The problem of inferring the evolutionary history and constructing the phylogenetic tree with high performance has become one of the major problems in computational biology.

Results: A new phylogenetic tree construction method from a given set of objects (proteins, species, etc.) is presented. As an extension of ant colony optimization, this method proposes an adaptive phylogenetic clustering algorithm based on a digraph to find a tree structure that defines the ancestral relationships among the given objects.

Conclusion: Our phylogenetic tree construction method is tested to compare its results with that of the genetic algorithm (GA). Experimental results show that …