Discovering lesser known molecular players and mechanistic patterns in Alzheimer's disease using an integrative disease modelling approach

Convergence of exponentially advancing technologies is driving medical research with life changing discoveries. On the contrary, repeated failures of high-profile drugs to battle Alzheimer's disease (AD) has made it one of the least successful therapeutic area. This failure pattern has provoked researchers to grapple with their beliefs about Alzheimer's aetiology. Thus, growing realisation that Amyloid-β and tau are not 'the' but rather 'one of the' factors necessitates the reassessment of pre-existing data to add new perspectives. To enable a holistic view of the disease, integrative modelling approaches are emerging as a powerful technique. Combining data at different scales and modes could considerably increase the predictive power of the integrative model by filling biological knowledge gaps. However, the reliability of the derived hypotheses largely depends on the completeness, quality, consistency, and context-specificity of the data. Thus, there is a need for agile methods and approaches that efficiently interrogate and utilise existing public data. This thesis presents the development of novel approaches and methods that address intrinsic issues of data integration and analysis in AD research. It aims to prioritise lesser-known AD candidates using highly curated and precise knowledge derived from integrated data. Here much of the emphasis is put on quality, reliability, and context-specificity. This thesis work showcases the benefit of integrating well-curated and disease-specific heterogeneous data in a semantic web-based framework for mining actionable knowledge. Furthermore, it introduces to the challenges encountered while harvesting information from literature and transcriptomic resources. State-of-the-art text-mining methodology is developed to extract miRNAs and its regulatory role in diseases and genes from the biomedical literature. To enable meta-analysis of biologically related transcriptomic data, a highly-curated metadata database has been developed, which explicates annotations specific to human and animal models. Finally, to corroborate common mechanistic patterns — embedded with novel candidates — across large-scale AD transcriptomic data, a new approach to generate gene regulatory networks has been developed. The work presented here has demonstrated its capability in identifying testable mechanistic hypotheses containing previously unknown or emerging knowledge from public data in two major publicly funded projects for Alzheimer's, Parkinson's and Epilepsy diseases

Semantics-driven Abstractive Document Summarization

The evolution of the Web over the last three decades has led to a deluge of scientific and news articles on the Internet. Harnessing these publications in different fields of study is critical to effective end user information consumption. Similarly, in the domain of healthcare, one of the key challenges with the adoption of Electronic Health Records (EHRs) for clinical practice has been the tremendous amount of clinical notes generated that can be summarized without which clinical decision making and communication will be inefficient and costly. In spite of the rapid advances in information retrieval and deep learning techniques towards abstractive document summarization, the results of these efforts continue to resemble extractive summaries, achieving promising results predominantly on lexical metrics but performing poorly on semantic metrics. Thus, abstractive summarization that is driven by intrinsic and extrinsic semantics of documents is not adequately explored. Resources that can be used for generating semantics-driven abstractive summaries include: • Abstracts of multiple scientific articles published in a given technical field of study to generate an abstractive summary for topically-related abstracts within the field, thus reducing the load of having to read semantically duplicate abstracts on a given topic. • Citation contexts from different authoritative papers citing a reference paper can be used to generate utility-oriented abstractive summary for a scientific article. • Biomedical articles and the named entities characterizing the biomedical articles along with background knowledge bases to generate entity and fact-aware abstractive summaries. • Clinical notes of patients and clinical knowledge bases for abstractive clinical text summarization using knowledge-driven multi-objective optimization. In this dissertation, we develop semantics-driven abstractive models based on intra- document and inter-document semantic analyses along with facts of named entities retrieved from domain-specific knowledge bases to produce summaries. Concretely, we propose a sequence of frameworks leveraging semantics at various granularity (e.g., word, sentence, document, topic, citations, and named entities) levels, by utilizing external resources. The proposed frameworks have been applied to a range of tasks including 1. Abstractive summarization of topic-centric multi-document scientific articles and news articles. 2. Abstractive summarization of scientific articles using crowd-sourced citation contexts. 3. Abstractive summarization of biomedical articles clustered based on entity-relatedness. 4. Abstractive summarization of clinical notes of patients with heart failure and Chest X-Rays recordings. The proposed approaches achieve impressive performance in terms of preserving semantics in abstractive summarization while paraphrasing. For summarization of topic-centric multiple scientific/news articles, we propose a three-stage approach where abstracts of scientific articles or news articles are clustered based on their topical similarity determined from topics generated using Latent Dirichlet Allocation (LDA), followed by extractive phase and abstractive phase. Then, in the next stage, we focus on abstractive summarization of biomedical literature where we leverage named entities in biomedical articles to 1) cluster related articles; and 2) leverage the named entities towards guiding abstractive summarization. Finally, in the last stage, we turn to external resources such as citation contexts pointing to a scientific article to generate a comprehensive and utility-centric abstractive summary of a scientific article, domain-specific knowledge bases to fill gaps in information about entities in a biomedical article to summarize and clinical notes to guide abstractive summarization of clinical text. Thus, the bottom-up progression of exploring semantics towards abstractive summarization in this dissertation starts with (i) Semantic Analysis of Latent Topics; builds on (ii) Internal and External Knowledge-I (gleaned from abstracts and Citation Contexts); and extends it to make it comprehensive using (iii) Internal and External Knowledge-II (Named Entities and Knowledge Bases)

Chemical Information Bulletin

Periodic supplement for "the regular journals of the American Chemical Society," containing annotated bibliographies of chemical documentation literature as well as information about meetings, conferences, awards, scholarships, and other news from the American Chemical Society (ACS) Division of Chemical Literature

Pacific Symposium on Biocomputing 2023

The Pacific Symposium on Biocomputing (PSB) 2023 is an international, multidisciplinary conference for the presentation and discussion of current research in the theory and application of computational methods in problems of biological significance. Presentations are rigorously peer reviewed and are published in an archival proceedings volume. PSB 2023 will be held on January 3-7, 2023 in Kohala Coast, Hawaii. Tutorials and workshops will be offered prior to the start of the conference.PSB 2023 will bring together top researchers from the US, the Asian Pacific nations, and around the world to exchange research results and address open issues in all aspects of computational biology. It is a forum for the presentation of work in databases, algorithms, interfaces, visualization, modeling, and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology.The PSB has been designed to be responsive to the need for critical mass in sub-disciplines within biocomputing. For that reason, it is the only meeting whose sessions are defined dynamically each year in response to specific proposals. PSB sessions are organized by leaders of research in biocomputing's 'hot topics.' In this way, the meeting provides an early forum for serious examination of emerging methods and approaches in this rapidly changing field

High-Performance Modelling and Simulation for Big Data Applications

This open access book was prepared as a Final Publication of the COST Action IC1406 “High-Performance Modelling and Simulation for Big Data Applications (cHiPSet)“ project. Long considered important pillars of the scientific method, Modelling and Simulation have evolved from traditional discrete numerical methods to complex data-intensive continuous analytical optimisations. Resolution, scale, and accuracy have become essential to predict and analyse natural and complex systems in science and engineering. When their level of abstraction raises to have a better discernment of the domain at hand, their representation gets increasingly demanding for computational and data resources. On the other hand, High Performance Computing typically entails the effective use of parallel and distributed processing units coupled with efficient storage, communication and visualisation systems to underpin complex data-intensive applications in distinct scientific and technical domains. It is then arguably required to have a seamless interaction of High Performance Computing with Modelling and Simulation in order to store, compute, analyse, and visualise large data sets in science and engineering. Funded by the European Commission, cHiPSet has provided a dynamic trans-European forum for their members and distinguished guests to openly discuss novel perspectives and topics of interests for these two communities. This cHiPSet compendium presents a set of selected case studies related to healthcare, biological data, computational advertising, multimedia, finance, bioinformatics, and telecommunications