PubMed and beyond: a survey of web tools for searching biomedical literature

The past decade has witnessed the modern advances of high-throughput technology and rapid growth of research capacity in producing large-scale biological data, both of which were concomitant with an exponential growth of biomedical literature. This wealth of scholarly knowledge is of significant importance for researchers in making scientific discoveries and healthcare professionals in managing health-related matters. However, the acquisition of such information is becoming increasingly difficult due to its large volume and rapid growth. In response, the National Center for Biotechnology Information (NCBI) is continuously making changes to its PubMed Web service for improvement. Meanwhile, different entities have devoted themselves to developing Web tools for helping users quickly and efficiently search and retrieve relevant publications. These practices, together with maturity in the field of text mining, have led to an increase in the number and quality of various Web tools that provide comparable literature search service to PubMed. In this study, we review 28 such tools, highlight their respective innovations, compare them to the PubMed system and one another, and discuss directions for future development. Furthermore, we have built a website dedicated to tracking existing systems and future advances in the field of biomedical literature search. Taken together, our work serves information seekers in choosing tools for their needs and service providers and developers in keeping current in the field

An intelligent search engine and GUI-based efficient MEDLINE search tool based on deep syntactic parsing

We present a practical HPSG parser for English, an intelligent search engine to retrieve MEDLINE abstracts that represent biomedical events and an efficient MED-LINE search tool helping users to find information about biomedical entities such as genes, proteins, and the interactions between them.

ARIANA: Adaptive Robust and Integrative Analysis for finding Novel Associations

The effective mining of biological literature can provide a range of services such as hypothesis-generation, semantic-sensitive information retrieval, and knowledge discovery, which can be important to understand the confluence of different diseases, genes, and risk factors. Furthermore, integration of different tools at specific levels could be valuable. The main focus of the dissertation is developing and integrating tools in finding network of semantically related entities. The key contribution is the design and implementation of an Adaptive Robust and Integrative Analysis for finding Novel Associations. ARIANA is a software architecture and a web-based system for efficient and scalable knowledge discovery. It integrates semantic-sensitive analysis of text-data through ontology-mapping with database search technology to ensure the required specificity. ARIANA was prototyped using the Medical Subject Headings ontology and PubMed database and has demonstrated great success as a dynamic-data-driven system. ARIANA has five main components: (i) Data Stratification, (ii) Ontology-Mapping, (iii) Parameter Optimized Latent Semantic Analysis, (iv) Relevance Model and (v) Interface and Visualization. The other contribution is integration of ARIANA with Online Mendelian Inheritance in Man database, and Medical Subject Headings ontology to provide gene-disease associations. Empirical studies produced some exciting knowledge discovery instances. Among them was the connection between the hexamethonium and pulmonary inflammation and fibrosis. In 2001, a research study at John Hopkins used the drug hexamethonium on a healthy volunteer that ended in a tragic death due to pulmonary inflammation and fibrosis. This accident might have been prevented if the researcher knew of published case report. Since the original case report in 1955, there has not been any publications regarding that association. ARIANA extracted this knowledge even though its database contains publications from 1960 to 2012. Out of 2,545 concepts, ARIANA ranked “Scleroderma, Systemic”, “Neoplasms, Fibrous Tissue”, “Pneumonia”, “Fibroma”, and “Pulmonary Fibrosis” as the 13th, 16th, 38th, 174th and 257th ranked concept respectively. The researcher had access to such knowledge this drug would likely not have been used on healthy subjects.In today\u27s world where data and knowledge are moving away from each other, semantic-sensitive tools such as ARIANA can bridge that gap and advance dissemination of knowledge

Biomedical Event Extraction with Machine Learning

Biomedical natural language processing (BioNLP) is a subfield of natural language processing, an area of computational linguistics concerned with developing programs that work with natural language: written texts and speech. Biomedical relation extraction concerns the detection of semantic relations such as protein-protein interactions (PPI) from scientific texts. The aim is to enhance information retrieval by detecting relations between concepts, not just individual concepts as with a keyword search. In recent years, events have been proposed as a more detailed alternative for simple pairwise PPI relations. Events provide a systematic, structural representation for annotating the content of natural language texts. Events are characterized by annotated trigger words, directed and typed arguments and the ability to nest other events. For example, the sentence “Protein A causes protein B to bind protein C” can be annotated with the nested event structure CAUSE(A, BIND(B, C)). Converted to such formal representations, the information of natural language texts can be used by computational applications. Biomedical event annotations were introduced by the BioInfer and GENIA corpora, and event extraction was popularized by the BioNLP'09 Shared Task on Event Extraction. In this thesis we present a method for automated event extraction, implemented as the Turku Event Extraction System (TEES). A unified graph format is defined for representing event annotations and the problem of extracting complex event structures is decomposed into a number of independent classification tasks. These classification tasks are solved using SVM and RLS classifiers, utilizing rich feature representations built from full dependency parsing. Building on earlier work on pairwise relation extraction and using a generalized graph representation, the resulting TEES system is capable of detecting binary relations as well as complex event structures. We show that this event extraction system has good performance, reaching the first place in the BioNLP'09 Shared Task on Event Extraction. Subsequently, TEES has achieved several first ranks in the BioNLP'11 and BioNLP'13 Shared Tasks, as well as shown competitive performance in the binary relation Drug-Drug Interaction Extraction 2011 and 2013 shared tasks. The Turku Event Extraction System is published as a freely available open-source project, documenting the research in detail as well as making the method available for practical applications. In particular, in this thesis we describe the application of the event extraction method to PubMed-scale text mining, showing how the developed approach not only shows good performance, but is generalizable and applicable to large-scale real-world text mining projects. Finally, we discuss related literature, summarize the contributions of the work and present some thoughts on future directions for biomedical event extraction. This thesis includes and builds on six original research publications. The first of these introduces the analysis of dependency parses that leads to development of TEES. The entries in the three BioNLP Shared Tasks, as well as in the DDIExtraction 2011 task are covered in four publications, and the sixth one demonstrates the application of the system to PubMed-scale text mining.Siirretty Doriast

A Knowledge-based Integrative Modeling Approach for <em>In-Silico</em> Identification of Mechanistic Targets in Neurodegeneration with Focus on Alzheimer’s Disease

Dementia is the progressive decline in cognitive function due to damage or disease in the body beyond what might be expected from normal aging. Based on neuropathological and clinical criteria, dementia includes a spectrum of diseases, namely Alzheimer's dementia, Parkinson's dementia, Lewy Body disease, Alzheimer's dementia with Parkinson's, Pick's disease, Semantic dementia, and large and small vessel disease. It is thought that these disorders result from a combination of genetic and environmental risk factors. Despite accumulating knowledge that has been gained about pathophysiological and clinical characteristics of the disease, no coherent and integrative picture of molecular mechanisms underlying neurodegeneration in Alzheimer’s disease is available. Existing drugs only offer symptomatic relief to the patients and lack any efficient disease-modifying effects. The present research proposes a knowledge-based rationale towards integrative modeling of disease mechanism for identifying potential candidate targets and biomarkers in Alzheimer’s disease. Integrative disease modeling is an emerging knowledge-based paradigm in translational research that exploits the power of computational methods to collect, store, integrate, model and interpret accumulated disease information across different biological scales from molecules to phenotypes. It prepares the ground for transitioning from ‘descriptive’ to “mechanistic” representation of disease processes. The proposed approach was used to introduce an integrative framework, which integrates, on one hand, extracted knowledge from the literature using semantically supported text-mining technologies and, on the other hand, primary experimental data such as gene/protein expression or imaging readouts. The aim of such a hybrid integrative modeling approach was not only to provide a consolidated systems view on the disease mechanism as a whole but also to increase specificity and sensitivity of the mechanistic model by providing disease-specific context. This approach was successfully used for correlating clinical manifestations of the disease to their corresponding molecular events and led to the identification and modeling of three important mechanistic components underlying Alzheimer’s dementia, namely the CNS, the immune system and the endocrine components. These models were validated using a novel in-silico validation method, namely biomarker-guided pathway analysis and a pathway-based target identification approach was introduced, which resulted in the identification of the MAPK signaling pathway as a potential candidate target at the crossroad of the triad components underlying disease mechanism in Alzheimer’s dementia