Methodological challenges and analytic opportunities for modeling and interpreting Big Healthcare Data

Abstract Managing, processing and understanding big healthcare data is challenging, costly and demanding. Without a robust fundamental theory for representation, analysis and inference, a roadmap for uniform handling and analyzing of such complex data remains elusive. In this article, we outline various big data challenges, opportunities, modeling methods and software techniques for blending complex healthcare data, advanced analytic tools, and distributed scientific computing. Using imaging, genetic and healthcare data we provide examples of processing heterogeneous datasets using distributed cloud services, automated and semi-automated classification techniques, and open-science protocols. Despite substantial advances, new innovative technologies need to be developed that enhance, scale and optimize the management and processing of large, complex and heterogeneous data. Stakeholder investments in data acquisition, research and development, computational infrastructure and education will be critical to realize the huge potential of big data, to reap the expected information benefits and to build lasting knowledge assets. Multi-faceted proprietary, open-source, and community developments will be essential to enable broad, reliable, sustainable and efficient data-driven discovery and analytics. Big data will affect every sector of the economy and their hallmark will be ‘team science’.http://deepblue.lib.umich.edu/bitstream/2027.42/134522/1/13742_2016_Article_117.pd

Concept graphs: Applications to biomedical text categorization and concept extraction

As science advances, the underlying literature grows rapidly providing valuable knowledge mines for researchers and practitioners. The text content that makes up these knowledge collections is often unstructured and, thus, extracting relevant or novel information could be nontrivial and costly. In addition, human knowledge and expertise are being transformed into structured digital information in the form of vocabulary databases and ontologies. These knowledge bases hold substantial hierarchical and semantic relationships of common domain concepts. Consequently, automating learning tasks could be reinforced with those knowledge bases through constructing human-like representations of knowledge. This allows developing algorithms that simulate the human reasoning tasks of content perception, concept identification, and classification. This study explores the representation of text documents using concept graphs that are constructed with the help of a domain ontology. In particular, the target data sets are collections of biomedical text documents, and the domain ontology is a collection of predefined biomedical concepts and relationships among them. The proposed representation preserves those relationships and allows using the structural features of graphs in text mining and learning algorithms. Those features emphasize the significance of the underlying relationship information that exists in the text content behind the interrelated topics and concepts of a text document. The experiments presented in this study include text categorization and concept extraction applied on biomedical data sets. The experimental results demonstrate how the relationships extracted from text and captured in graph structures can be used to improve the performance of the aforementioned applications. The discussed techniques can be used in creating and maintaining digital libraries through enhancing indexing, retrieval, and management of documents as well as in a broad range of domain-specific applications such as drug discovery, hypothesis generation, and the analysis of molecular structures in chemoinformatics

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

Unsupervised Biomedical Named Entity Recognition

Named entity recognition (NER) from text is an important task for several applications, including in the biomedical domain. Supervised machine learning based systems have been the most successful on NER task, however, they require correct annotations in large quantities for training. Annotating text manually is very labor intensive and also needs domain expertise. The purpose of this research is to reduce human annotation effort and to decrease cost of annotation for building NER systems in the biomedical domain. The method developed in this work is based on leveraging the availability of resources like UMLS (Unified Medical Language System), that contain a list of biomedical entities and a large unannotated corpus to build an unsupervised NER system that does not require any manual annotations. The method that we developed in this research has two phases. In the first phase, a biomedical corpus is automatically annotated with some named entities using UMLS through unambiguous exact matching which we call weakly-labeled data. In this data, positive examples are the entities in the text that exactly match in UMLS and have only one semantic type which belongs to the desired entity class to be extracted (for example, diseases and disorders). Negative examples are the entities in the text that exactly match in UMLS but are of semantic types other than those that belong to the desired entity class. These examples are then used to train a machine learning classifier using features that represent the contexts in which they appeared in the text. The trained classifier is applied back to the text to gather more examples iteratively through the process of self-training. The trained classifier is then capable of classifying mentions in an unseen text as of the desired entity class or not from the contexts in which they appear. Although the trained named entity detector is good at detecting the presence of entities of the desired class in text, it cannot determine their correct boundaries. In the second phase of our method, called “Boundary Expansion”, the correct boundaries of the entities are determined. This method is based on a novel idea that utilizes machine learning and UMLS. Training examples for boundary expansion are gathered directly from UMLS and do not require any manual annotations. We also developed a new WordNet based approach for boundary expansion. Our developed method was evaluated on three datasets - SemEval 2014 Task 7 dataset that has diseases and disorders as the desired entity class, GENIA dataset that has proteins, DNAs, RNAs, cell types, and cell lines as the desired entity classes, and i2b2 dataset that has problems, tests, and treatments as the desired entity classes. Our method performed well and obtained performance close to supervised methods on the SemEval dataset. On the other datasets, it outperformed an existing unsupervised method on most entity classes. Availability of a list of entity names with their semantic types and a large unannotated corpus are the only requirements of our method to work well. Given these, our method generalizes across different types of entities and different types of biomedical text. Being unsupervised, the method can be easily applied to new NER tasks without needing costly annotations

A novel gluten knowledge base of potential biomedical and health-related interactions extracted from the literature: using machine learning and graph analysis methodologies to reconstruct the bibliome

Background In return for their nutritional properties and broad availability, cereal crops have been associated with different alimentary disorders and symptoms, with the majority of the responsibility being attributed to gluten. Therefore, the research of gluten-related literature data continues to be produced at ever-growing rates, driven in part by the recent exploratory studies that link gluten to non-traditional diseases and the popularity of gluten-free diets, making it increasingly difficult to access and analyse practical and structured information. In this sense, the accelerated discovery of novel advances in diagnosis and treatment, as well as exploratory studies, produce a favourable scenario for disinformation and misinformation. Objectives Aligned with, the European Union strategy “Delivering on EU Food Safety and Nutrition in 2050″ which emphasizes the inextricable links between imbalanced diets, the increased exposure to unreliable sources of information and misleading information, and the increased dependency on reliable sources of information; this paper presents GlutKNOIS, a public and interactive literature-based database that reconstructs and represents the experimental biomedical knowledge extracted from the gluten-related literature. The developed platform includes different external database knowledge, bibliometrics statistics and social media discussion to propose a novel and enhanced way to search, visualise and analyse potential biomedical and health-related interactions in relation to the gluten domain. Methods For this purpose, the presented study applies a semi-supervised curation workflow that combines natural language processing techniques, machine learning algorithms, ontology-based normalization and integration approaches, named entity recognition methods, and graph knowledge reconstruction methodologies to process, classify, represent and analyse the experimental findings contained in the literature, which is also complemented by data from the social discussion. Results and conclusions In this sense, 5814 documents were manually annotated and 7424 were fully automatically processed to reconstruct the first online gluten-related knowledge database of evidenced health-related interactions that produce health or metabolic changes based on the literature. In addition, the automatic processing of the literature combined with the knowledge representation methodologies proposed has the potential to assist in the revision and analysis of years of gluten research. The reconstructed knowledge base is public and accessible at https://sing-group.org/glutknois/Fundação para a Ciência e a Tecnologia | Ref. UIDB/50006/2020Xunta de Galicia | Ref. ED481B-2019-032Xunta de Galicia | Ref. ED431G2019/06Xunta de Galicia | Ref. ED431C 2022/03Universidade de Vigo/CISU

Investigating Genotype-Phenotype relationship extraction from biomedical text

During the last decade biomedicine has developed at a tremendous pace. Every day a lot of biomedical papers are published and a large amount of new information is produced. To help enable automated and human interaction in the multitude of applications of this biomedical data, the need for Natural Language Processing systems to process the vast amount of new information is increasing. Our main purpose in this research project is to extract the relationships between genotypes and phenotypes mentioned in the biomedical publications. Such a system provides important and up-to-date data for database construction and updating, and even text summarization. To achieve this goal we had to solve three main problems: finding genotype names, finding phenotype names, and finally extracting phenotype--genotype interactions. We consider all these required modules in a comprehensive system and propose a promising solution for each of them taking into account available tools and resources. BANNER, an open source biomedical named entity recognition system, which has achieved good results in detecting genotypes, has been used for the genotype name recognition task. We were the first group to start working on phenotype name recognition. We have developed two different systems (rule-based and machine-learning based) for extracting phenotype names from text. These systems incorporated the available knowledge from the Unified Medical Language System metathesaurus and the Human Phenotype Onotolgy (HPO). As there was no available annotated corpus for phenotype names, we created a valuable corpus with annotated phenotype names using information available in HPO and a self-training method which can be used for future research. To solve the final problem of this project i.e. , phenotype--genotype relationship extraction, a machine learning method has been proposed. As there was no corpus available for this task and it was not possible for us to annotate a sufficiently large corpus manually, a semi-automatic approach has been used to annotate a small corpus and a self-training method has been proposed to annotate more sentences and enlarge this corpus. A test set was manually annotated by an expert. In addition to having phenotype-genotype relationships annotated, the test set contains important comments about the nature of these relationships. The evaluation results related to each system demonstrate the significantly good performance of all the proposed methods

Ontology Enrichment from Free-text Clinical Documents: A Comparison of Alternative Approaches

While the biomedical informatics community widely acknowledges the utility of domain ontologies, there remain many barriers to their effective use. One important requirement of domain ontologies is that they achieve a high degree of coverage of the domain concepts and concept relationships. However, the development of these ontologies is typically a manual, time-consuming, and often error-prone process. Limited resources result in missing concepts and relationships, as well as difficulty in updating the ontology as domain knowledge changes. Methodologies developed in the fields of Natural Language Processing (NLP), Information Extraction (IE), Information Retrieval (IR), and Machine Learning (ML) provide techniques for automating the enrichment of ontology from free-text documents. In this dissertation, I extended these methodologies into biomedical ontology development. First, I reviewed existing methodologies and systems developed in the fields of NLP, IR, and IE, and discussed how existing methods can benefit the development of biomedical ontologies. This previously unconducted review was published in the Journal of Biomedical Informatics. Second, I compared the effectiveness of three methods from two different approaches, the symbolic (the Hearst method) and the statistical (the Church and Lin methods), using clinical free-text documents. Third, I developed a methodological framework for Ontology Learning (OL) evaluation and comparison. This framework permits evaluation of the two types of OL approaches that include three OL methods. The significance of this work is as follows: 1) The results from the comparative study showed the potential of these methods for biomedical ontology enrichment. For the two targeted domains (NCIT and RadLex), the Hearst method revealed an average of 21% and 11% new concept acceptance rates, respectively. The Lin method produced a 74% acceptance rate for NCIT; the Church method, 53%. As a result of this study (published in the Journal of Methods of Information in Medicine), many suggested candidates have been incorporated into the NCIT; 2) The evaluation framework is flexible and general enough that it can analyze the performance of ontology enrichment methods for many domains, thus expediting the process of automation and minimizing the likelihood that key concepts and relationships would be missed as domain knowledge evolves

AI in drug discovery and its clinical relevance

The COVID-19 pandemic has emphasized the need for novel drug discovery process. However, the journey from conceptualizing a drug to its eventual implementation in clinical settings is a long, complex, and expensive process, with many potential points of failure. Over the past decade, a vast growth in medical information has coincided with advances in computational hardware (cloud computing, GPUs, and TPUs) and the rise of deep learning. Medical data generated from large molecular screening profiles, personal health or pathology records, and public health organizations could benefit from analysis by Artificial Intelligence (AI) approaches to speed up and prevent failures in the drug discovery pipeline. We present applications of AI at various stages of drug discovery pipelines, including the inherently computational approaches of de novo design and prediction of a drug's likely properties. Open-source databases and AI-based software tools that facilitate drug design are discussed along with their associated problems of molecule representation, data collection, complexity, labeling, and disparities among labels. How contemporary AI methods, such as graph neural networks, reinforcement learning, and generated models, along with structure-based methods, (i.e., molecular dynamics simulations and molecular docking) can contribute to drug discovery applications and analysis of drug responses is also explored. Finally, recent developments and investments in AI-based start-up companies for biotechnology, drug design and their current progress, hopes and promotions are discussed in this article.  Other InformationPublished in:HeliyonLicense: https://creativecommons.org/licenses/by/4.0/See article on publisher's website: https://doi.org/10.1016/j.heliyon.2023.e17575 </p