Finding Complex Biological Relationships in Recent PubMed Articles Using Bio-LDA

The overwhelming amount of available scholarly literature in the life sciences poses significant challenges to scientists wishing to keep up with important developments related to their research, but also provides a useful resource for the discovery of recent information concerning genes, diseases, compounds and the interactions between them. In this paper, we describe an algorithm called Bio-LDA that uses extracted biological terminology to automatically identify latent topics, and provides a variety of measures to uncover putative relations among topics and bio-terms. Relationships identified using those approaches are combined with existing data in life science datasets to provide additional insight. Three case studies demonstrate the utility of the Bio-LDA model, including association predication, association search and connectivity map generation. This combined approach offers new opportunities for knowledge discovery in many areas of biology including target identification, lead hopping and drug repurposing.Comment: 14 pages, 8 figures, 10 table

MOLIERE: Automatic Biomedical Hypothesis Generation System

Hypothesis generation is becoming a crucial time-saving technique which allows biomedical researchers to quickly discover implicit connections between important concepts. Typically, these systems operate on domain-specific fractions of public medical data. MOLIERE, in contrast, utilizes information from over 24.5 million documents. At the heart of our approach lies a multi-modal and multi-relational network of biomedical objects extracted from several heterogeneous datasets from the National Center for Biotechnology Information (NCBI). These objects include but are not limited to scientific papers, keywords, genes, proteins, diseases, and diagnoses. We model hypotheses using Latent Dirichlet Allocation applied on abstracts found near shortest paths discovered within this network, and demonstrate the effectiveness of MOLIERE by performing hypothesis generation on historical data. Our network, implementation, and resulting data are all publicly available for the broad scientific community

MOLIERE: Automatic Biomedical Hypothesis Generation System

Hypothesis generation is becoming a crucial time-saving technique which allows biomedical researchers to quickly discover implicit connections between important concepts. Typically, these systems operate on domain-specific fractions of public medical data. MOLIERE, in contrast, utilizes information from over 24.5 million documents. At the heart of our approach lies a multi-modal and multi-relational network of biomedical objects extracted from several heterogeneous datasets from the National Center for Biotechnology Information (NCBI). These objects include but are not limited to scientific papers, keywords, genes, proteins, diseases, and diagnoses. We model hypotheses using Latent Dirichlet Allocation applied on abstracts found near shortest paths discovered within this network, and demonstrate the effectiveness of MOLIERE by performing hypothesis generation on historical data. Our network, implementation, and resulting data are all publicly available for the broad scientific community

Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients.

Sputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heterogeneous mixtures of human cells and exogenous (microbial) material. In this study, we develop a pipeline that integrates dimensionality reduction and statistical modeling to grapple with the heterogeneity. LDA(Latent Dirichlet allocation)-link connects microbes to genes using reduced-dimensionality LDA topics. We validate our method with single-cell RNA-seq and microscopy and then apply it to the sputum of asthmatic patients to find known and novel relationships between microbes and genes

On mining latent treatment patterns from electronic medical records

Clinical pathway (CP) analysis plays an important role in health-care management in ensuring specialized, standardized, normalized and sophisticated therapy procedures for individual patients. Recently, with the rapid development of hospital information systems, a large volume of electronic medical records (EMRs) has been produced, which provides a comprehensive source for CP analysis. In this paper, we are concerned with the problem of utilizing the heterogeneous EMRs to assist CP analysis and improvement. More specifically, we develop a probabilistic topic model to link patient features and treatment behaviors together to mine treatment patterns hidden in EMRs. Discovered treatment patterns, as actionable knowledge representing the best practice for most patients in most time of their treatment processes, form the backbone of CPs, and can be exploited to help physicians better understand their specialty and learn from previous experiences for CP analysis and improvement. Experimental results on a real collection of 985 EMRs collected from a Chinese hospital show that the proposed approach can effectively identify meaningful treatment patterns from EMRs

Automated Discovery of Functional Generality of Human Gene Expression Programs

An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in the numbers of programs and sample populations, and temporal behavior. We developed GeneProgram, a new unsupervised computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular expression analysis methods. We applied GeneProgram to a compendium of 62 short time-series gene expression datasets exploring the responses of human cells to infectious agents and immune-modulating molecules. GeneProgram produced a map of 104 expression programs, a substantial number of which were significantly enriched for genes involved in key signaling pathways and/or bound by NF-κB transcription factors in genome-wide experiments. Further, GeneProgram discovered expression programs that appear to implicate surprising signaling pathways or receptor types in the response to infection, including Wnt signaling and neurotransmitter receptors. We believe the discovered map of expression programs involved in the response to infection will be useful for guiding future biological experiments; genes from programs with low generality scores might serve as new drug targets that exhibit minimal “cross-talk,” and genes from high generality programs may maintain common physiological responses that go awry in disease states. Further, our method is multipurpose, and can be applied readily to novel compendia of biological data

Exploiting Latent Features of Text and Graphs

As the size and scope of online data continues to grow, new machine learning techniques become necessary to best capitalize on the wealth of available information. However, the models that help convert data into knowledge require nontrivial processes to make sense of large collections of text and massive online graphs. In both scenarios, modern machine learning pipelines produce embeddings --- semantically rich vectors of latent features --- to convert human constructs for machine understanding. In this dissertation we focus on information available within biomedical science, including human-written abstracts of scientific papers, as well as machine-generated graphs of biomedical entity relationships. We present the Moliere system, and our method for identifying new discoveries through the use of natural language processing and graph mining algorithms. We propose heuristically-based ranking criteria to augment Moliere, and leverage this ranking to identify a new gene-treatment target for HIV-associated Neurodegenerative Disorders. We additionally focus on the latent features of graphs, and propose a new bipartite graph embedding technique. Using our graph embedding, we advance the state-of-the-art in hypergraph partitioning quality. Having newfound intuition of graph embeddings, we present Agatha, a deep-learning approach to hypothesis generation. This system learns a data-driven ranking criteria derived from the embeddings of our large proposed biomedical semantic graph. To produce human-readable results, we additionally propose CBAG, a technique for conditional biomedical abstract generation

Trends in COVID-19 Publications: Streamlining Research Using NLP and LDA.

Background: Research publications related to the novel coronavirus disease COVID-19 are rapidly increasing. However, current online literature hubs, even with artificial intelligence, are limited in identifying the complexity of COVID-19 research topics. We developed a comprehensive Latent Dirichlet Allocation (LDA) model with 25 topics using natural language processing (NLP) techniques on PubMed® research articles about "COVID." We propose a novel methodology to develop and visualise temporal trends, and improve existing online literature hubs. Our results for temporal evolution demonstrate interesting trends, for example, the prominence of "Mental Health" and "Socioeconomic Impact" increased, "Genome Sequence" decreased, and "Epidemiology" remained relatively constant. Applying our methodology to LitCovid, a literature hub from the National Center for Biotechnology Information, we improved the breadth and depth of research topics by subdividing their pre-existing categories. Our topic model demonstrates that research on "masks" and "Personal Protective Equipment (PPE)" is skewed toward clinical applications with a lack of population-based epidemiological research

Structure and agency in the economics of public policy for TB control

Globally, Tuberculosis remains a devastating disease, despite the availability of treatment. The disease is associated with poverty, and those with the disease incur a high cost of accessing care, while simultaneously experiencing income loss due to a loss in productivity. A key challenge in TB programmes remains the accurate diagnosis of the disease, especially in people who are HIV positive. Diagnosing TB can be very resource intensive and the accuracy of diagnosis is dependent on a range of disease, health service organisation and provider behaviour factors. This thesis seeks to enhance understanding of how the behaviour of healthcare workers mediates the value of TB diagnostic algorithms, and how this may affect the costs, outcomes as well as the economic burden associated with the disease in South Africa. The work presented is based on empirical work done alongside a pragmatic cluster randomized control trial. Empirically, it examines the longitudinal economic burden of TB diagnosis and treatment in South Africa. The discrepancies between the time at which patients incur the greatest cost and income loss, and the available social protection are highlighted. Based on empirical work, a purpose-built state-transition mathematical model of TB diagnosis and treatment was developed to estimate the cost-effectiveness, from the perspective of the health service and the patient, of health systems interventions to strengthen TB diagnosis. Recognising healthcare workers as those who ultimately express policies, the behaviour of healthcare workers was included in the cost-effectiveness analysis by 1) using data from a pragmatic trial reflecting routine practice and clinical decision-making at the time of the study; 2) developing a conceptual framework of the relationship between behaviour at decision points and disease outcomes; and 3) investigating how these interactions may influence the value of the diagnostic algorithm. Possible public policy levers to improve TB diagnosis in healthcare facilities, as well as the potential mediators of costs and effects were explored. The thesis concludes with recommendations for further methodological work to expand on the approach explored in this thesis to improve how heterogeneity in estimates of cost-effectiveness is presented to decision-makers