Assumption 0 analysis: comparative phylogenetic studies in the age of complexity

Darwin's panoramic view of biology encompassed two metaphors: the phylogenetic tree, pointing to relatively linear (and divergent) complexity, and the tangled bank, pointing to reticulated (and convergent) complexity. The emergence of phylogenetic systematics half a century ago made it possible to investigate linear complexity in biology. Assumption 0, first proposed in 1986, is not needed for cases of simple evolutionary patterns, but must be invoked when there are complex evolutionary patterns whose hallmark is reticulated relationships. A corollary of Assumption 0, the duplication convention, was proposed in 1990, permitting standard phylogenetic systematic ontology to be used in discovering reticulated evolutionary histories. In 2004, a new algorithm, phylogenetic analysis for comparing trees (PACT), was developed specifically for use in analyses invoking Assumption 0. PACT can help discern complex evolutionary explanations for historical biogeographical, coevolutionary, phylogenetic, and tokogenetic processe

Supporting software processes analysis and decision-making using provenance data

Data provenance can be defined as the description of the origins of a piece of data and the process by which it arrived in a database. Provenance has been successfully used in health sciences, chemical industries, and scientific computing, considering that these areas require a comprehensive traceability mechanism. Moreover, companies have been increasing the amount of data they collect from their systems and processes, considering the dropping cost of memory and storage technologies in the last years. Thus, this thesis investigates if the use of provenance models and techniques can support software processes execution analysis and data-driven decision-making, considering the increasing availability of process data provided by companies. A provenance model for software processes was developed and evaluated by experts in process and provenance area, in addition to an approach for capturing, storing, inferencing of implicit information, and visualization to software process provenance data. In addition, a case study using data from industry’s processes was conducted to evaluate the approach, with a discussion about several specific analysis and data-driven decision-making possibilities.Proveniência de dados é definida como a descrição da origem de um dado e o processo pelo qual este passou até chegar ao seu estado atual. Proveniência de dados tem sido usada com sucesso em domínios como ciências da saúde, indústrias químicas e computação científica, considerando que essas áreas exigem um mecanismo abrangente de rastreabilidade. Por outro lado, as empresas vêm aumentando a quantidade de dados que coletam de seus sistemas e processos, considerando a diminuição no custo das tecnologias de memória e armazenamento nos últimos anos. Assim, esta tese investiga se o uso de modelos e técnicas de proveniência é capaz de apoiar a análise da execução de processos de software e a tomada de decisões baseada em dados, considerando a disponibilização cada vez maior de dados relativos a processos pelas empresas. Um modelo de proveniência para processos de software foi desenvolvido e avaliado por especialistas em processos e proveniência, além de uma abordagem e ferramental de apoio para captura, armazenamento, inferência de novas informações e posterior análise e visualização dos dados de proveniência de processos. Um estudo de caso utilizando dados de processos da indústria foi conduzido para avaliação da abordagem e discussão de possibilidades distintas para análise e tomada de decisão orientada por estes dados

Discovering information from an integrated graph database

The information explosion in science has become a different problem, not the sheer amount per se, but the multiplicity and heterogeneity of massive sets of data sources. Relations mined from these heterogeneous sources, namely texts, database records, and ontologies have been mapped to Resource Description Framework (RDF) triples in an integrated database. The subject and object resources are expressed as references to concepts in a biomedical ontology consisting of the Unified Medical Language System (UMLS), UniProt and EntrezGene and for the predicate resource to a predicate thesaurus. All RDF triples have been stored in a graph database, including provenance. For evaluation we used an actual formal PRISMA literature study identifying 61 cerebral spinal fluid biomarkers and 200 blood biomarkers for migraine. These biomarkers sets could be retrieved with weighted mean average precision values of 0.32 and 0.59, respectively, and can be used as a first reference for further refinements

Computational Toxinology

Venoms are complex mixtures of biological macromolecules and other compounds that are used for predatory and defensive purposes by hundreds of thousands of known species worldwide. Throughout human history, venoms and venom components have been used to treat a vast array of illnesses, causing them to be of great clinical, economic, and academic interest to the drug discovery and toxinology communities. In spite of major computational advances that facilitate data-driven drug discovery, most therapeutic venom effects are still discovered via tedious trial-and-error, or simply by accident. In this dissertation, I describe a body of work that aims to establish a new subdiscipline of translational bioinformatics, which I name “computational toxinology”. To accomplish this goal, I present three integrated components that span a wide range of informatics techniques: (1) VenomKB, (2) VenomSeq, and (3) VenomKB’s Semantic API. To provide a platform for structuring, representing, retrieving, and integrating venom data relevant to drug discovery, VenomKB provides a database-backed web application and knowledge base for computational toxinology. VenomKB is structured according to a fully-featured ontology of venoms, and provides data aggregated from many popular web re- sources. VenomSeq is a biotechnology workflow that is designed to generate new high-throughput sequencing data for incorporation into VenomKB. Specifically, we expose human cells to controlled doses of crude venoms, conduct RNA-Sequencing, and build profiles of differential gene expression, which we then compare to publicly-available differential expression data for known dis- eases and drugs with known effects, and use those comparisons to hypothesize ways that the venoms could act in a therapeutic manner, as well. These data are then integrated into VenomKB, where they can be effectively retrieved and evaluated using existing data and known therapeutic associations. VenomKB’s Semantic API further develops this functionality by providing an intelligent, powerful, and user-friendly interface for querying the complex underlying data in VenomKB in a way that reflects the intuitive, human-understandable mean- ing of those data. The Semantic API is designed to cater to the needs of advanced users as well as laypersons and bench scientists without previous expertise in computational biology and semantic data analysis. In each chapter of the dissertation, I describe how we evaluated these 3 components through various approaches. We demonstrate the utility of VenomKB and the Semantic API by testing a number of practical use-cases for each, designed to highlight their ability to rediscover existing knowledge as well as suggesting potential areas for future exploration. We use statistics and data science techniques to evaluate VenomSeq on 25 diverse species of venomous animals, and propose biologically feasible explanations for significant findings. In evaluating the Semantic API, I show how observations on VenomSeq data can be interpreted and placed into the context of past research by members of the larger toxinology community. Computational toxinology is a toolbox designed to be used by multiple stakeholders (toxinologists, computational biologists, and systems pharmacologists, among others) to improve the return rate of clinically-significant findings from manual experimentation. It aims to achieve this goal by enabling access to data, providing means for easy validation of results, and suggesting specific hypotheses that are preliminarily supported by rigorous inferential statistics. All components of the research I describe are open-access and publicly available, to improve reproducibility and encourage widespread adoptio

Knowledge-based Biomedical Data Science 2019

Knowledge-based biomedical data science (KBDS) involves the design and implementation of computer systems that act as if they knew about biomedicine. Such systems depend on formally represented knowledge in computer systems, often in the form of knowledge graphs. Here we survey the progress in the last year in systems that use formally represented knowledge to address data science problems in both clinical and biological domains, as well as on approaches for creating knowledge graphs. Major themes include the relationships between knowledge graphs and machine learning, the use of natural language processing, and the expansion of knowledge-based approaches to novel domains, such as Chinese Traditional Medicine and biodiversity.Comment: Manuscript 43 pages with 3 tables; Supplemental material 43 pages with 3 table

Social Search with Missing Data: Which Ranking Algorithm?

Online social networking tools are extremely popular, but can miss potential discoveries latent in the social 'fabric'. Matchmaking services which can do naive profile matching with old database technology are too brittle in the absence of key data, and even modern ontological markup, though powerful, can be onerous at data-input time. In this paper, we present a system called BuddyFinder which can automatically identify buddies who can best match a user's search requirements specified in a term-based query, even in the absence of stored user-profiles. We deploy and compare five statistical measures, namely, our own CORDER, mutual information (MI), phi-squared, improved MI and Z score, and two TF/IDF based baseline methods to find online users who best match the search requirements based on 'inferred profiles' of these users in the form of scavenged web pages. These measures identify statistically significant relationships between online users and a term-based query. Our user evaluation on two groups of users shows that BuddyFinder can find users highly relevant to search queries, and that CORDER achieved the best average ranking correlations among all seven algorithms and improved the performance of both baseline methods

Mixed membership stochastic blockmodels

Observations consisting of measurements on relationships for pairs of objects arise in many settings, such as protein interaction and gene regulatory networks, collections of author-recipient email, and social networks. Analyzing such data with probabilisic models can be delicate because the simple exchangeability assumptions underlying many boilerplate models no longer hold. In this paper, we describe a latent variable model of such data called the mixed membership stochastic blockmodel. This model extends blockmodels for relational data to ones which capture mixed membership latent relational structure, thus providing an object-specific low-dimensional representation. We develop a general variational inference algorithm for fast approximate posterior inference. We explore applications to social and protein interaction networks.Comment: 46 pages, 14 figures, 3 table