The Infectious Disease Ontology in the Age of COVID-19

The Infectious Disease Ontology (IDO) is a suite of interoperable ontology modules that aims to provide coverage of all aspects of the infectious disease domain, including biomedical research, clinical care, and public health. IDO Core is designed to be a disease and pathogen neutral ontology, covering just those types of entities and relations that are relevant to infectious diseases generally. IDO Core is then extended by a collection of ontology modules focusing on specific diseases and pathogens. In this paper we present applications of IDO Core within various areas of infectious disease research, together with an overview of all IDO extension ontologies and the methodology on the basis of which they are built. We also survey recent developments involving IDO, including the creation of IDO Virus; the Coronaviruses Infectious Disease Ontology (CIDO); and an extension of CIDO focused on COVID-19 (IDO-CovID-19).We also discuss how these ontologies might assist in information-driven efforts to deal with the ongoing COVID-19 pandemic, to accelerate data discovery in the early stages of future pandemics, and to promote reproducibility of infectious disease research

A Survey on Interpretable Cross-modal Reasoning

In recent years, cross-modal reasoning (CMR), the process of understanding and reasoning across different modalities, has emerged as a pivotal area with applications spanning from multimedia analysis to healthcare diagnostics. As the deployment of AI systems becomes more ubiquitous, the demand for transparency and comprehensibility in these systems' decision-making processes has intensified. This survey delves into the realm of interpretable cross-modal reasoning (I-CMR), where the objective is not only to achieve high predictive performance but also to provide human-understandable explanations for the results. This survey presents a comprehensive overview of the typical methods with a three-level taxonomy for I-CMR. Furthermore, this survey reviews the existing CMR datasets with annotations for explanations. Finally, this survey summarizes the challenges for I-CMR and discusses potential future directions. In conclusion, this survey aims to catalyze the progress of this emerging research area by providing researchers with a panoramic and comprehensive perspective, illuminating the state of the art and discerning the opportunities

Setting the basis of best practices and standards for curation and annotation of logical models in biology

International audienceThe fast accumulation of biological data calls for their integration, analysis and exploitation through more systematic approaches. The generation of novel, relevant hypotheses from this enormous quantity of data remains challenging. Logical models have long been used to answer a variety of questions regarding the dynamical behaviours of regulatory networks. As the number of published logical models increases, there is a pressing need for systematic model annotation, referencing and curation in community-supported and standardised formats. This article summarises the key topics and future directions of a meeting entitled ‘Annotation and curation of computational models in biology’, organised as part of the 2019 [BC]2 conference. The purpose of the meeting was to develop and drive forward a plan towards the standardised annotation of logical models, review and connect various ongoing projects of experts from different communities involved in the modelling and annotation of molecular biological entities, interactions, pathways and models. This article defines a roadmap towards the annotation and curation of logical models, including milestones for best practices and minimum standard requirements

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

Development of Integrated Machine Learning and Data Science Approaches for the Prediction of Cancer Mutation and Autonomous Drug Discovery of Anti-Cancer Therapeutic Agents

Few technological ideas have captivated the minds of biochemical researchers to the degree that machine learning (ML) and artificial intelligence (AI) have. Over the last few years, advances in the ML field have driven the design of new computational systems that improve with experience and are able to model increasingly complex chemical and biological phenomena. In this dissertation, we capitalize on these achievements and use machine learning to study drug receptor sites and design drugs to target these sites. First, we analyze the significance of various single nucleotide variations and assess their rate of contribution to cancer. Following that, we used a portfolio of machine learning and data science approaches to design new drugs to target protein kinase inhibitors. We show that these techniques exhibit strong promise in aiding cancer research and drug discovery

Proceedings, MSVSCC 2018

Proceedings of the 12th Annual Modeling, Simulation & Visualization Student Capstone Conference held on April 19, 2018 at VMASC in Suffolk, Virginia. 155 pp

Developing eThread pipeline using SAGA-pilot abstraction for large-scale structural bioinformatics

While most of computational annotation approaches are sequence-based, threading methods are becoming increasingly attractive because of predicted structural information that could uncover the underlying function. However, threading tools are generally compute-intensive and the number of protein sequences from even small genomes such as prokaryotes is large typically containing many thousands, prohibiting their application as a genome-wide structural systems biology tool. To leverage its utility, we have developed a pipeline for eThread - a meta-threading protein structure modeling tool, that can use computational resources efficiently and effectively. We employ a pilot-based approach that supports seamless data and task-level parallelism and manages large variation in workload and computational requirements. Our scalable pipeline is deployed on Amazon EC2 and can efficiently select resources based upon task requirements. We present runtime analysis to characterize computational complexity of eThread and EC2 infrastructure. Based on results, we suggest a pathway to an optimized solution with respect to metrics such as time-to-solution or cost-to-solution. Our eThread pipeline can scale to support a large number of sequences and is expected to be a viable solution for genome-scale structural bioinformatics and structure-based annotation, particularly, amenable for small genomes such as prokaryotes. The developed pipeline is easily extensible to other types of distributed cyberinfrastructure. © 2014 Anjani Ragothaman et al

Standardizing New Diagnostic Tests to Facilitate Rapid Responses to The Covid-19 Pandemic

In order to enhance the data interoperability, an expeditious and accurate standardization solution is highly desirable for naming rapidly emerging novel lab tests, and thus diminishes confusion in early responses to pandemic outbreaks. This is a preliminary study to explore the roles and implementation of medical informatics technology, especially natural language processing and ontology methods, in standardizing information about emerging lab tests during a pandemic, thereby facilitating rapid responses to the pandemic. The ultimate goal of this study is to develop an informatics framework for rapid standardization of lab testing names during a pandemic to better prepare for future public health threats. We first constructed an information model for lab tests approved during the COVID-19 pandemic and built a named entity recognition tool that can automatically extract lab test information specified in the information model from the Emergency Use Authorization(EUA)documents of the U.S. Food and Drug Administration (FDA), thus creating a catalog of approved lab tests with detailed information. To facilitate the standardization of lab testing data in electronic health records, we further developed the COVID-19 TestNorm, a tool that normalizes the names of various COVID-19 lab testing used by different healthcare facilities into standard Logical Observation Identifiers Names and Codes (LOINC). The overall accuracy of COVID-19 TestNorm on the development set was 98.9%, and on the independent test set was 97.4%. Lastly, we conducted a clinical study on COVID-19 re-positivity to demonstrate the utility of standardized lab test information in supporting clinical research. We believe that the result of my study indicates great a potential of medical informatics technologies for facilitating rapid responses to both current and future pandemics

Computational strategies to combat COVID-19: useful tools to accelerate SARS-CoV-2 and coronavirus research

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are free to use and available online, either through web applications or public code repositories.Peer Reviewe

Implementation of an hybrid machine learning methodology for pharmacological modeling

Tese de mestrado, Bioinformática e Biologia Computacional (Bioinformática) Universidade de Lisboa, Faculdade de Ciências, 2017Hoje em dia, especialmente na area biomedica, os dados contem milhares de variaveis de fontes diferentes e com apenas algumas instancias ao mesmo tempo. Devido a este facto, as abordagens da aprendizagem automatica enfrentam dois problemas, nomeadamente a questao da integracao de dados heterogeneos e a selecao das caracteristicas. Este trabalho propoe uma solucao eficiente para esta questao e proporciona uma implementacao funcional da metodologia hibrida. A inspiracao para este trabalho veio do desafio proposto no ambito da competicao AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge em 2016, e da solucao vencedora desenvolvida por Yuanfang Guan. Relativamente a motivacao do concurso, e observado que os tratamentos combinatorios para o cancro sao mais eficientes do que as terapias habituais de agente unico, desde que tem potencial para superar as desvantagens dos outros (limitado espetro de acao e desenvolvimento de resistencia). No entanto, o efeito combinatorio de drogas nao e obvio, produzindo possivelmente o resultado aditivo, sinergico ou antagonico. Assim, o objetivo da competicao era prever in vitro a sinergia dos compostos, sem ter acesso aos dados experimentais da terapia combinatoria. No ambito da competicao foram fornecidos ficheiros de varias fontes, contendo o conhecimento farmacologico tanto experimental como obtido de ajustamento das equacoes, a informacao sobre propriedades quimicas e estruturais de drogas, e por fim, os perfis moleculares de celulas, incluindo expressao de RNA, copy variants, sequencia e metilacao de DNA. O trabalho referido envolveu uma abordagem muito bem sucedida de integração dos dados heterogeneos, estendendo o modelo com conhecimento disponivel dentro do projeto The Cancer Cell Line Encyclopedia, e tambem introduzindo o passo decisivo de simulacao que permite imitar o efeito de terapia combinatoria no cancro. Apesar das descricoes pouco claras e da documentacao da solucao vencedora ineficiente, a reproducao da abordagem de Guan foi concluida, tentando ser o mais fiel possivel. A implementacao funcional foi escrita nas linguagens R e Python, e o seu desempenho foi verificado usando como referencia a matriz submetida no concurso. Para melhorar a metodologia, o workflow de selecao dos caracteristicas foi estabelecido e executado usando o algoritmo Lasso. Alem disso, o desempenho de dois metodos alternativos de modelacao foi experimentado, incluindo Support Vector Machine and Multivariate Adaptive Regression Splines (MARS). Varias versoes da equacao de integracao foram consideradas permitindo a determinacao de coeficientes aparentemente otimos. Como resultado, a compreensao da melhor solucao de competição foi desenvolvida e a implementacao funcional foi construida com sucesso. As melhorias foram propostas e no efeito o algoritmo SVM foi verificado como capaz de superar os outros na resolução deste problema, a equacao de integracao com melhor desempenho foi estabelecida e finalmente a lista de 75 variaveis moleculares mais informativas foi fornecida. Entre estes genes, poderiam ser encontrados possiveis candidatos de biomarcadores de cancro.Nowadays, especially in the biomedical field, the data sets usually contain thousands of multi-source variables and with only few instances in the same time. Due to this fact, Machine Learning approaches face two problems, namely the issue of heterogenous data integration and the feature selection. This work proposes an efficient solution for this question and provides a functional implementation of the hybrid methodology. The inspiration originated from the AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge from 2016 and the winning solution by Yuanfang Guan. Regarding to the motivation of competition, the combinatory cancer treatments are believed to be more effective than standard single-agent therapies since they have a potential to overcome others weaknesses (narrow spectrum of action and development of the resistance). However, the combinatorial drug effect is not obvious bringing possibly additive, synergistic or antagonistic treatment result. Thus, the goal of the competition was to predict in vitro compound synergy, without the access to the experimental combinatory therapy data. Within the competition, the multi-source files were supplied, encompassing the pharmacological knowledge from experiments and equation-fitting, the information on chemical properties and structure of drugs, finally the molecular cell profiles including RNA expression, copy variants, DNA sequence and methylation. The referred work included very successful approach of heterogenous data integration, extending additionally the model with prior knowledge outsourced from The Cancer Cell Line Encyclopedia, as well as introduced a key step of simulation that allows to imitate effect of a combinatory therapy on cancer. Despite unexplicit descriptions and poor documentation of the winning solution, as accurate as possible, reproduction of Guan’s approach was accomplished. The functional implementation was written in R and Python languages, and its performance was verified using as a reference the submitted in challenge prediction matrix. In order to improve the methodology feature selection workflow was established and run using a Lasso algorithm. Moreover, the performance of two alternative modeling methods was experimented including Support Vector Machine and Multivariate Adaptive Regression Splines (MARS). Several versions of merging equation were considered allowing determination of apparently optimal coefficients. As the result, the understanding of the best challenge solution was developed and the functional implementation was successfully constructed. The improvements were proposed and in the effect the SVM algorithm was verified to surpass others in solving this problem, the best-performing merging equation was established, and finally the list of 75 most informative molecular variables was provided. Among those genes, potential cancer biomarker candidates could be found