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Bada, M.

Publications and source records attributed to Bada, M..

4 recordsLinked to original sources

Hypothesizing mechanistic links between microbes and disease using knowledge graphs

Knowledge graphs have found broad biomedical applications, providing useful representations of complex knowledge. Although plentiful evidence exists linking the gut microbiome to disease, mechanistic understanding of those relationships remains generally elusive. Here we demonstrate the potential of knowledge graphs to hypothesize plausible mechanistic accounts of host-microbe interactions in disease. To do so, we constructed a knowledge graph of linked microbes, genes and metabolites called MGMLink. Using a semantically constrained shortest path search through the graph and a novel path prioritization methodology based on cosine similarity, we show that this knowledge supports inference of mechanistic hypotheses that explain observed relationships between microbes and disease phenotypes. We discuss specific applications of this methodology in inflammatory bowel disease and Parkinsons disease. This approach enables mechanistic hypotheses surrounding the complex interactions between gut microbes and disease to be generated in a scalable and comprehensive manner.

bioinformatics↗

Creating an Ignorance-Base: Exploring Known Unknowns in the Scientific Literature

BackgroundScientific discovery progresses by exploring new and uncharted territory. More specifically, it advances by a process of transforming unknown unknowns first into known unknowns, and then into knowns. Over the last few decades, researchers have developed many knowledge bases to capture and connect the knowns, which has enabled topic exploration and contextualization of experimental results. But recognizing the unknowns is also critical for finding the most pertinent questions and their answers. Prior work on known unknowns has sought to understand them, annotate them, and automate their identification. However, no knowledge-bases yet exist to capture these unknowns, and little work has focused on how scientists might use them to trace a given topic or experimental result in search of open questions and new avenues for exploration. We show here that a knowledge base of unknowns can be connected to ontologically grounded biomedical knowledge to accelerate research in the field of prenatal nutrition. ResultsWe present the first ignorance-base, a knowledge-base created by combining classifiers to recognize ignorance statements (statements of missing or incomplete knowledge that imply a goal for knowledge) and biomedical concepts over the prenatal nutrition literature. This knowledge-base places biomedical concepts mentioned in the literature in context with the ignorance statements authors have made about them. Using our system, researchers interested in the topic of vitamin D and prenatal health were able to uncover three new avenues for exploration (immune system, respiratory system, and brain development), which were buried among the many standard enriched concepts, by searching for concepts enriched in ignorance statements. Additionally, we used the ignorance-base to enrich concepts connected to a gene list associated with vitamin D and spontaneous preterm birth and found an emerging topic of study (brain development) in an implied field (neuroscience). The researchers could look to the field of neuroscience for potential answers to the ignorance statements. ConclusionOur goal is to help students, researchers, funders, and publishers better understand the state of our collective scientific ignorance (known unknowns) in order to help accelerate research through the continued illumination of and focus on the known unknowns and their respective goals for scientific knowledge. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/519634v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1edb6e6org.highwire.dtl.DTLVardef@182bf3corg.highwire.dtl.DTLVardef@d90312org.highwire.dtl.DTLVardef@1589433_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe created the first ignorance-base (knowledge-base) to capture goals for scientific knowledge C_LIO_LIOur exploration methods provide analyses, summaries, and visualizations based on a query C_LIO_LIIgnorance enrichment provided fruitful avenues for future research C_LIO_LIExploration by topic in vitamin D found three avenues to explore C_LIO_LIExploration by experimental results for vitamin D and preterm birth found an emerging topic C_LI

bioinformatics↗

Concept Recognition as a Machine Translation Problem

BackgroundAutomated assignment of specific ontology concepts to mentions in text is a critical task in biomedical natural language processing, and the subject of many open shared tasks. Although the current state of the art involves the use of neural network language models as a post-processing step, the very large number of ontology classes to be recognized and the limited amount of gold-standard training data has impeded the creation of end-to-end systems based entirely on machine learning. Recently, Hailu et al. recast the concept recognition problem as a type of machine translation and demonstrated that sequence-to-sequence machine learning models had the potential to outperform multi-class classification approaches. Here we systematically characterize the factors that contribute to the accuracy and efficiency of several approaches to sequence-to-sequence machine learning. ResultsWe report on our extensive studies of alternative methods and hyperparameter selections. The results not only identify the best-performing systems and parameters across a wide variety of ontologies but also illuminate about the widely varying resource requirements and hyperparameter robustness of alternative approaches. Analysis of the strengths and weaknesses of such systems suggest promising avenues for future improvements as well as design choices that can increase computational efficiency with small costs in performance. Bidirectional Encoder Representations from Transformers for Biomedical Text Mining (BioBERT) for span detection (as previously found) along with the Open-source Toolkit for Neural Machine Translation (OpenNMT) for concept normalization achieve state-of-the-art performance for most ontologies in CRAFT Corpus. This approach uses substantially fewer computational resources, including hardware, memory, and time than several alternative approaches. ConclusionsMachine translation is a promising avenue for fully machine-learning-based concept recognition that achieves state-of-the-art results on the CRAFT Corpus, evaluated via a direct comparison to previous results from the 2019 CRAFT Shared Task. Experiments illuminating the reasons for the surprisingly good performance of sequence-to-sequence methods targeting ontology identifiers suggest that further progress may be possible by mapping to alternative target concept representations. All code and models can be found at: https://github.com/UCDenver-ccp/Concept-Recognition-as-Translation.

bioinformatics↗

Biomedical Concept Recognition Using Deep Neural Sequence Models

Backgroundthe automated identification of mentions of ontological concepts in natural language texts is a central task in biomedical information extraction. Despite more than a decade of effort, performance in this task remains below the level necessary for many applications. Resultsrecently, applications of deep learning in natural language processing have demonstrated striking improvements over previously state-of-the-art performance in many related natural language processing tasks. Here we demonstrate similarly striking performance improvements in recognizing biomedical ontology concepts in full text journal articles using deep learning techniques originally developed for machine translation. For example, our best performing system improves the performance of the previous state-of-the-art in recognizing terms in the Gene Ontology Biological Process hierarchy, from a previous best F1 score of 0.40 to an F1 of 0.70, nearly halving the error rate. Nearly all other ontologies show similar performance improvements. ConclusionsA two-stage concept recognition system, which is a conditional random field model for span detection followed by a deep neural sequence model for normalization, improves the state-of-the-art performance for biomedical concept recognition. Treating the biomedical concept normalization task as a sequence-to-sequence mapping task similar to neural machine translation improves performance.

bioinformatics↗