Download or read book Improvements in Machine Learning for Predicting Taxon Phenotype and Function from Genetic Sequences written by Zhengqiao Zhao and published by . This book was released on 2020 with total page 219 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in DNA sequencing, as well as the rise of shotgun metagenomics and metabolomics, are rapidly producing complex microbiome datasets for studies of human health and the environment. The large-scale sampling of DNA/RNA from microbes provides a window into the microbiome's interactions with its host and habitat, enables us to predict phenotypic traits of the host/microbiome, aids the discovery of emergent biological function, and supports the medical diagnosis. Researchers try to extract features from DNA/RNA sequencing data and make 1) taxonomic predictions ("Who is there"), 2) function annotations ("What they are doing") and 3) host/microbiome phenotype predictions. This work is to explore different computational methods to address challenges in these three fields. First, taxonomic classification relies on NCBI RefSeq database sequences, which are being added at an exponential rate. Therefore, the incremental learning concept is especially important. Although the incremental naive Bayes classifier (NBC) is a decade old concept, it has not been applied to taxonomic classification in the metagenomics field. In this work, I compare the classification accuracy and runtime of the proposed incremental learning implementation of NBC with the performance of the traditional implementation of NBC and demonstrate a proof of concept of how incremental learning can make taxonomic classification much more efficient in its training process, significantly reducing computation while maintaining accuracy. In addition to predicting taxonomic labels for metagenomic samples, researchers are also interested in identifying different subtypes for one virus since mutations can be introduced during the transmission. "Oligotyping" is an entropy analysis tool developed for subtyping taxonomic units based on 16S rRNA sequences. "Oligotyping" was formulated because the 16S rRNA gene is very conservative and there are only very few mutations in the 16S rRNA gene for some lineages. The SARS-CoV-2 genome, being months old, also has a relatively small amount of mutations. Therefore, the entropy analysis developed for 16S rRNA sequences can be adapted for SARS-CoV-2 viral genome subtyping. However, other researchers were only looking at sequence similarity (and subsequent trees) or important single nucleotide variants individually between the genomes. To my knowledge, I am the first to draw on the "Oligotyping" concept to group mutations as a "barcode" of the viral genome and extend it to define subtypes for SARS-CoV-2 viral genomes. I further add error correction to account for ambiguities in the sequences and, optionally, apply further compression by identifying patterns of base entropy correlation. I demonstrate its application in spatiotemporal analyses of real world SARS-CoV-2 sequences responsible for the COVID-19 pandemic. My method is validated by comparing the subtypes defined to similar subtypes discovered in other literature. Third, microbial survey data is not used efficiently for phenotype prediction. For example, a precise Crohn's disease prediction model can help diagnostics given stool samples collected from subjects. To predict Crohn's disease (or another phenotype) from microbiome composition, researchers usually start by grouping sequences that look similar together into an Operation Taxonomic Unit (OTU) or Amplicon Sequence Variant (ASV) and subsequently learn samples by examining OTU occurrences in different phenotypes. However, only looking at sequence similarity ignores the sequential information contained in DNA sequences. Bioinformatics has been inspired by successes in deep learning applications in Natural Language Processing (NLP). Both convolutional neural network (CNN) and recurrent neural network (RNN) have been utilized to learn DNA sequential information for applications such as transcription factor binding site classification. In my work, I propose to adapt deep learning architectures (such as RNN and attention mechanism) that have been widely used in NLP to develop a "phenotype" classifier. This Read2Pheno classifier can predict "phenotype" based on 16S rRNA reads. I demonstrate how the sequential information learned by the proposed model can provide insights on informative regions in DNA sequences/reads while making accurate predictions. The model is validated by comparing its accuracy with other baseline methods such as a random forest model trained with various features (standard OTU/ASV table and k-mers). Forth, there have been different deep learning based functional annotation models proposed recently. However, these models can only output one class of function annotation predictions, such as Gene Ontology (GO). It is convenient to have a tool that can output function predictions for both function annotation databases. In this work, I first extend the proposed Read2Pheno model to a function prediction model, AttentionGO, and compare the performance with both alignment based and deep learning based models to show that the proposed model can achieve comparable performance with additional interpretability. Second, I explore the possibility of using the proposed AttentionGO classifier in a multi-task learning model to predict three branches of GO terms and KEGG Orthology terms simultaneously. The multi-task learning model is compared with single-task models trained with individual tasks to demonstrate performance improvement.

Download or read book Handbook of Machine Learning Applications for Genomics written by Sanjiban Sekhar Roy and published by Springer Nature. This book was released on 2022-06-23 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt: Currently, machine learning is playing a pivotal role in the progress of genomics. The applications of machine learning are helping all to understand the emerging trends and the future scope of genomics. This book provides comprehensive coverage of machine learning applications such as DNN, CNN, and RNN, for predicting the sequence of DNA and RNA binding proteins, expression of the gene, and splicing control. In addition, the book addresses the effect of multiomics data analysis of cancers using tensor decomposition, machine learning techniques for protein engineering, CNN applications on genomics, challenges of long noncoding RNAs in human disease diagnosis, and how machine learning can be used as a tool to shape the future of medicine. More importantly, it gives a comparative analysis and validates the outcomes of machine learning methods on genomic data to the functional laboratory tests or by formal clinical assessment. The topics of this book will cater interest to academicians, practitioners working in the field of functional genomics, and machine learning. Also, this book shall guide comprehensively the graduate, postgraduates, and Ph.D. scholars working in these fields.

Download or read book Machine Learning for Microbial Phenotype Prediction written by Roman Feldbauer and published by Springer. This book was released on 2016-06-15 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis presents a scalable, generic methodology for microbial phenotype prediction based on supervised machine learning, several models for biological and ecological traits of high relevance, and the deployment in metagenomic datasets. The results suggest that the presented prediction tool can be used to automatically annotate phenotypes in near-complete microbial genome sequences, as generated in large numbers in current metagenomic studies. Unraveling relationships between a living organism's genetic information and its observable traits is a central biological problem. Phenotype prediction facilitated by machine learning techniques will be a major step forward to creating biological knowledge from big data.

Download or read book Machine Learning Models for Functional Genomics and Therapeutic Design written by Haoyang Zeng (Ph.D.) and published by . This book was released on 2019 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt: Due to the limited size of training data available, machine learning models for biology have remained rudimentary and inaccurate despite the significant advance in machine learning research. With the recent advent of high-throughput sequencing technology, an exponentially growing number of genomic and proteomic datasets have been generated. These large-scale datasets admit the training of high-capacity machine learning models to characterize sophisticated features and produce accurate predictions on unseen examples. In this thesis, we attempt to develop advanced machine learning models for functional genomics and therapeutics design, two areas with ample data deposited in public databases and tremendous clinical implications. The shared theme of these models is to learn how the composition of a biological sequence encodes a functional phenotype and then leverage such knowledge to provide insight for target discovery and therapeutic design. First, we design three machine learning models that predict transcription factor binding and DNA methylation, two fundamental epigenetic phenotypes closely tied to gene regulation, from DNA sequence alone. We show that these epigenetic phenotypes can be well predicted from the sequence context. Moreover, the predicted change in phenotype between the reference and alternate allele of a genetic variant accurately reflect its functional impact and improves the identification of regulatory variants causal for complex diseases. Second, we devise two machine learning models that improve the prediction of peptides displayed by the major histocompatibility complex (MHC) on the cell surface. Computational modeling of peptide-display by MHC is central in the design of peptide-based therapeutics. Our first machine learning model introduces the capacity to quantify uncertainty in the computational prediction and proposes a new metric for peptide prioritization that reduces false positives in high-affinity peptide design. The second model improves the state-of-the-art performance in MHC-ligand prediction by employing a deep language model to learn the sequence determinants for auxiliary processes in MHC-ligand selection, such as proteasome cleavage, that are omitted by existing methods due to the lack of labeled data. Third, we develop machine learning frameworks to model the enrichment of an antibody sequence in phage-panning experiments against a target antigen. We show that antibodies with low specificity can be reduced by a computational procedure using machine learning models trained for multiple targets. Moreover, machine learning can help to design novel antibody sequences with improved affinity.

Download or read book Interpretable Machine Learning Methods for Regulatory and Disease Genomics written by Peyton Greis Greenside and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: It is an incredible feat of nature that the same genome contains the code to every cell in each living organism. From this same genome, each unique cell type gains a different program of gene expression that enables the development and function of an organism throughout its lifespan. The non-coding genome - the ~98 of the genome that does not code directly for proteins - serves an important role in generating the diverse programs of gene expression turned on in each unique cell state. A complex network of proteins bind specific regulatory elements in the non-coding genome to regulate the expression of nearby genes. While basic principles of gene regulation are understood, the regulatory code of which factors bind together at which genomic elements to turn on which genes remains to be revealed. Further, we do not understand how disruptions in gene regulation, such as from mutations that fall in non-coding regions, ultimately lead to disease or other changes in cell state. In this work we present several methods developed and applied to learn the regulatory code or the rules that govern non-coding regions of the genome and how they regulate nearby genes. We first formulate the problem as one of learning pairs of sequence motifs and expressed regulator proteins that jointly predict the state of the cell, such as the cell type specific gene expression or chromatin accessibility. Using pre-engineered sequence features and known expression, we use a paired-feature boosting approach to build an interpretable model of how the non-coding genome contributes to cell state. We also demonstrate a novel improvement to this method that takes into account similarities between closely related cell types by using a hierarchy imposed on all of the predicted cell states. We apply this method to discover validated regulators of tadpole tail regeneration and to predict protein-ligand binding interactions. Recognizing the need for improved sequence features and stronger predictive performance, we then move to a deep learning modeling framework to predict epigenomic phenotypes such as chromatin accessibility from just underlying DNA sequence. We use deep learning models, specifically multi-task convolutional neural networks, to learn a featurization of sequences over several kilobases long and their mapping to a functional phenotype. We develop novel architectures that encode principles of genomics in models typically designed for computer vision, such as incorporating reverse complementation and the 3D structure of the genome. We also develop methods to interpret traditionally ``black box" neural networks by 1) assigning importance scores to each input sequence to the model, 2) summarizing non-redundant patterns learned by the model that are predictive in each cell type, and 3) discovering interactions learned by the model that provide indications as to how different non-coding sequence features depend on each other. We apply these methods in the system of hematopoiesis to interpret chromatin dynamics across differentiation of blood cell types, to understand immune stimulation, and to interpret immune disease-associated variants that fall in non-coding regions. We demonstrate strong performance of our boosting and deep learning models and demonstrate improved performance of these machine learning frameworks when taking into account existing knowledge about the biological system being modeled. We benchmark our interpretation methods using gold standard systems and existing experimental data where available. We confirm existing knowledge surrounding essential factors in hematopoiesis, and also generate novel hypotheses surrounding how factors interact to regulate differentiation. Ultimately our work provides a set of tools for researchers to probe and understand the non-coding genome and its role in controlling gene expression as well as a set of novel insights surrounding how hematopoiesis is controlled on many scales from global quantification of regulatory sequence to interpretation of individual variants.

Download or read book Machine Learning Techniques on Gene Function Prediction written by Quan Zou and published by Frontiers Media SA. This book was released on 2019-12-04 with total page 485 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Artificial Intelligence written by Marco Antonio Aceves-Fernandez and published by BoD – Books on Demand. This book was released on 2018-06-27 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: Artificial intelligence (AI) is taking an increasingly important role in our society. From cars, smartphones, airplanes, consumer applications, and even medical equipment, the impact of AI is changing the world around us. The ability of machines to demonstrate advanced cognitive skills in taking decisions, learn and perceive the environment, predict certain behavior, and process written or spoken languages, among other skills, makes this discipline of paramount importance in today's world. Although AI is changing the world for the better in many applications, it also comes with its challenges. This book encompasses many applications as well as new techniques, challenges, and opportunities in this fascinating area.

Download or read book Defining the Characteristics and Roles of Functional Genomic Sequences Using Computational Approaches written by John P. Lloyd and published by . This book was released on 2017 with total page 209 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Machine Learning for the Study of Gene Regulation and Complex Traits written by Anne Sonnenschein and published by . This book was released on 2017 with total page 151 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Machine Learning Approaches to Biological Sequence and Phenotype Data Analysis written by Renqiang Min and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Biologically Interpretable Machine Learning Methods to Understand Gene Regulation for Disease Phenotypes written by Ting Jin and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene expression and regulation is a key molecular mechanism driving the development of human diseases, particularly at the cell type level, but it remains elusive. For example in many brain diseases, such as Alzheimer's disease (AD), understanding how cell-type gene expression and regulation change across multiple stages of AD progression is still challenging. Moreover, interindividual variability of gene expression and regulation is a known characteristic of the human brain and brain diseases. However, it is still unclear how interindividual variability affects personalized gene regulation in brain diseases including AD, thereby contributing to their heterogeneity. Recent technological advances have enabled the detection of gene regulation activities through multi-omics (i.e., genomics, transcriptomics, epigenomics, proteomics). In particular, emerging single-cell sequencing technologies (e.g., scRNA-seq, scATAC-seq) allow us to study functional genomics and gene regulation at the cell-type level. Moreover, these multi-omics data of populations (e.g., human individuals) provide a unique opportunity to study the underlying regulatory mechanisms occurring in brain disease progression and clinical phenotypes. For instance, PsychAD is a large project generating single-cell multi-omics data including many neuronal and glial cell types, aiming to understand the molecular mechanisms of neuropsychiatric symptoms of multiple brain diseases (e.g., AD, SCZ, ASD, Bipolar) from over 1,000 individuals. However, analyzing and integrating large-scale multi-omics data at the population level, as well as understanding the mechanisms of gene regulation, also remains a challenge. Machine learning is a powerful and emerging tool to decode the unique complexities and heterogeneity of human diseases. For instance, Beebe-Wang, Nicosia, et al. developed MD-AD, a multi-task neural network model to predict various disease phenotypes in AD patients using RNA-seq. Additionally, with advancements in graph neural networks, which possess enhanced capabilities to represent sophisticated gene network structures like gene regulation networks that control gene expression. Efforts have also been made to capture the gene regulation heterogeneity of brain diseases. For instance, Kim SY has applied graph convolutional networks to offer personalized diagnostic insights through population graphs that correspond with disease progression. However, many existing machine learning methods are often limited to constructing accurate models for disease phenotype prediction and frequently lack biological interpretability or personalized insights, especially in gene regulation. Therefore, to address these challenges, my Ph.D. works have developed three machine-learning methods designed to decode the gene regulation mechanisms of human diseases. First, in this dissertation, I will present scGRNom, a computational pipeline that integrates multi-omic data to construct cell-type gene regulatory networks (GRNs) linking non-coding regulatory elements. Next, I will introduce i-BrainMap an interpretable knowledge-guided graph neural network model to prioritize personalized cell type disease genes, regulatory linkages, and modules. Thirdly, I introduce ECMaker, a semi-restricted Boltzmann machine (semi-RBM) method for identifying gene networks to predict diseases and clinical phenotypes. Overall, all our interpretable machine learning models improve phenotype prediction, prioritize key genes and networks associated with disease phenotypes, and are further aimed at enhancing our understanding of gene regulatory mechanisms driving disease progression and clinical phenotypes.

Download or read book Predicting Engineering and Interpreting Gene Regulatory Sequences and Proteins with Deep Learning written by Johannes Staffan Anders Linder and published by . This book was released on 2021 with total page 112 pages. Available in PDF, EPUB and Kindle. Book excerpt: The vast majority of the 3.1 billion base-pairs in the (haploid) human genome do not code for a particular protein, yet mutations in these non-coding regions can have a profound impact on phenotype and be deleterious. The reason is that within these regions - enhancers, promoters, introns and untranslated regions (UTRs) - reside a cis-regulatory code which governs gene expression and is sensitive to disruption. Ongoing efforts of mapping the relationship between genetic variants and disease phenotype are limited by data and the lack of generalizability. Furthermore, engineering \textit{de novo} gene-regulatory sequences and proteins according to target specifications, which would aid the development of vaccines, medical therapeutics, molecular sensing devices and more, is hampered by the lack of methods that can reliably generate large sets of diverse and optimized candidate designs for high-throughput screening. This dissertation presents an approach combining Massively Parallel Reporter Assays (MPRAs) with Deep Learning to obtain a sequence-predictive model of Alternative Polyadenylation (APA), a regulatory process occurring mainly in the 3' UTR of pre-mRNA. The trained neural network predicts 3'-end cleavage at base-pair resolution and can accurately prioritize human variants. By developing methods to visualize features learned in higher-order network layers, we extract a cis-regulatory APA code that aligns well with established biology. Next, the dissertation presents a family of methods that were developed to design de novo biological sequences based on the response of a differentiable fitness predictor. These methods, which are based on activation maximization, can be used to efficiently generate millions of diverse, optimized sequence designs on the basis of a deep generative model. Finally, we present a feature attribution method for interpreting neural network predictions. The method, which learns input masks that either reconstruct or destroy the prediction, implements a masking operator based on probabilistic sampling that is shown to be particularly well-suited for interpreting biological sequence models. The developed design- and interpretation methods are demonstrated on several DNA-, RNA- and protein function predictors and outperform state-of-the-art methods for multiple target applications.

Download or read book Deep Learning in Biology and Medicine written by Davide Bacciu and published by World Scientific Publishing Europe Limited. This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biology, medicine and biochemistry have become data-centric fields for which Deep Learning methods are delivering groundbreaking results. Addressing high impact challenges, Deep Learning in Biology and Medicine provides an accessible and organic collection of Deep Learning essays on bioinformatics and medicine. It caters for a wide readership, ranging from machine learning practitioners and data scientists seeking methodological knowledge to address biomedical applications, to life science specialists in search of a gentle reference for advanced data analytics.With contributions from internationally renowned experts, the book covers foundational methodologies in a wide spectrum of life sciences applications, including electronic health record processing, diagnostic imaging, text processing, as well as omics-data processing. This survey of consolidated problems is complemented by a selection of advanced applications, including cheminformatics and biomedical interaction network analysis. A modern and mindful approach to the use of data-driven methodologies in the life sciences also requires careful consideration of the associated societal, ethical, legal and transparency challenges, which are covered in the concluding chapters of this book.

Download or read book Advances in Cell and Molecular Diagnostics written by P.B. Raghavendra and published by Academic Press. This book was released on 2018-01-02 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Cell and Molecular Diagnostics brings the scientific advances in the translation and validation of cellular and molecular discoveries in medicine into the clinical diagnostic setting. It enumerates the description and application of technological advances in the field of cellular and molecular diagnostic medicine, providing an overview of specialized fields, such as biomarker, genetic marker, screening, DNA-profiling, NGS, cytogenetics, transcriptome, cancer biomarkers, prostate specific antigen, and biomarker toxicologies. In addition, it presents novel discoveries and clinical pathologic correlations, including studies in oncology, infectious diseases, inherited diseases, predisposition to disease, and the description or polymorphisms linked to disease states. This book is a valuable resource for oncologists, practitioners and several members of the biomedical field who are interested in understanding how to apply cutting-edge technologies into diagnostics and healthcare. Encompasses the current scientific advances in the translation and validation of cellular and molecular discoveries into the clinical diagnostic setting Explains the application of cellular and molecular diagnostics methodologies in clinical trials Focuses on translating preclinical tests to the bedside in order to help readers apply the most recent technologies to healthcare

Download or read book Graph Representation Learning written by William L. William L. Hamilton and published by Springer Nature. This book was released on 2022-06-01 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: Graph-structured data is ubiquitous throughout the natural and social sciences, from telecommunication networks to quantum chemistry. Building relational inductive biases into deep learning architectures is crucial for creating systems that can learn, reason, and generalize from this kind of data. Recent years have seen a surge in research on graph representation learning, including techniques for deep graph embeddings, generalizations of convolutional neural networks to graph-structured data, and neural message-passing approaches inspired by belief propagation. These advances in graph representation learning have led to new state-of-the-art results in numerous domains, including chemical synthesis, 3D vision, recommender systems, question answering, and social network analysis. This book provides a synthesis and overview of graph representation learning. It begins with a discussion of the goals of graph representation learning as well as key methodological foundations in graph theory and network analysis. Following this, the book introduces and reviews methods for learning node embeddings, including random-walk-based methods and applications to knowledge graphs. It then provides a technical synthesis and introduction to the highly successful graph neural network (GNN) formalism, which has become a dominant and fast-growing paradigm for deep learning with graph data. The book concludes with a synthesis of recent advancements in deep generative models for graphs—a nascent but quickly growing subset of graph representation learning.

Download or read book Precision Medicine and Artificial Intelligence written by Michael Mahler and published by Academic Press. This book was released on 2021-03-12 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: Precision Medicine and Artificial Intelligence: The Perfect Fit for Autoimmunity covers background on artificial intelligence (AI), its link to precision medicine (PM), and examples of AI in healthcare, especially autoimmunity. The book highlights future perspectives and potential directions as AI has gained significant attention during the past decade. Autoimmune diseases are complex and heterogeneous conditions, but exciting new developments and implementation tactics surrounding automated systems have enabled the generation of large datasets, making autoimmunity an ideal target for AI and precision medicine. More and more diagnostic products utilize AI, which is also starting to be supported by regulatory agencies such as the Food and Drug Administration (FDA). Knowledge generation by leveraging large datasets including demographic, environmental, clinical and biomarker data has the potential to not only impact the diagnosis of patients, but also disease prediction, prognosis and treatment options. Allows the readers to gain an overview on precision medicine for autoimmune diseases leveraging AI solutions Provides background, milestone and examples of precision medicine Outlines the paradigm shift towards precision medicine driven by value-based systems Discusses future applications of precision medicine research using AI Other aspects covered in the book include regulatory insights, data analytics and visualization, types of biomarkers as well as the role of the patient in precision medicine

Download or read book Basic Concepts and Recent Advances in Microbial Diversity Taxonomy Speciation and Evolution written by Suchitra Godbole and published by Cambridge Scholars Publishing. This book was released on 2024-03-05 with total page 414 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book delves into the fundamental principles that underpin the classification and understanding of bacteria, from the basic concepts to the latest advances. This book encompasses numerous topics related to diversity, such as speciation and evolution of species, microbial diversity, and methods for estimating diversity and taxonomy of bacteria. The reader can gain valuable insights into the cutting-edge techniques used to identify and classify bacteria, such as genomics, metagenomics, and phylogenetic analysis. With expert contributions from leading scientists, this comprehensive guide offers a holistic view of the microbial world in the context of their role in global biodiversity, and explores the upcoming role of machine learning and artificial intelligence for exploration of bacterial diversity. For students and researchers in microbiology, genetics and biotechnology, this book is an essential resource for unravelling the mysteries of bacterial speciation, evolution, diversity, and taxonomy.