Hypotheses Generation as Supervised Link Discovery with Automated Class Lebeling on Large-scale Biomedical Concept Networks (original) (raw)
Related papers
BMC Genomics, 2012
Computational approaches to generate hypotheses from biomedical literature have been studied intensively in recent years. Nevertheless, it still remains a challenge to automatically discover novel, cross-silo biomedical hypotheses from large-scale literature repositories. In order to address this challenge, we first model a biomedical literature repository as a comprehensive network of biomedical concepts and formulate hypotheses generation as a process of link discovery on the concept network. We extract the relevant information from the biomedical literature corpus and generate a concept network and concept-author map on a cluster using Map-Reduce framework. We extract a set of heterogeneous features such as random walk based features, neighborhood features and common author features. The potential number of links to consider for the possibility of link discovery is large in our concept network and to address the scalability problem, the features from a concept network are extracted using a cluster with Map-Reduce framework. We further model link discovery as a classification problem carried out on a training data set automatically extracted from two network snapshots taken in two consecutive time duration. A set of heterogeneous features, which cover both topological and semantic features derived from the concept network, have been studied with respect to their impacts on the accuracy of the proposed supervised link discovery process. A case study of hypotheses generation based on the proposed method has been presented in the paper.
Bridging Concept Identification for Constructing Information Networks from Text Documents
Lecture Notes in Computer Science, 2012
A major challenge for next generation data mining systems is creative knowledge discovery from diverse and distributed data sources. In this task an important challenge is information fusion of diverse mainly unstructured representations into a unique knowledge format. This chapter focuses on merging information available in text documents into an information network-a graph representation of knowledge. The problem addressed is how to efficiently and effectively produce an information network from large text corpora from at least two diverse, seemingly unrelated, domains. The goal is to produce a network that has the highest potential for providing yet unexplored cross-domain links which could lead to new scientific discoveries. The focus of this work is better identification of important domain-bridging concepts that are promoted as core nodes around which the rest of the network is formed. The evaluation is performed by repeating a discovery made on medical articles in the migraine-magnesium domain.
Context-driven automatic subgraph creation for literature-based discovery
Background: Literature-based discovery (LBD) is characterized by uncovering hidden associations in non-interacting scientific literature. Prior approaches to LBD include use of: (1) domain expertise and struc-tured background knowledge to manually filter and explore the literature, (2) distributional statistics and graph-theoretic measures to rank interesting connections, and (3) heuristics to help eliminate spurious connections. However, manual approaches to LBD are not scalable and purely distributional approaches may not be sufficient to obtain insights into the meaning of poorly understood associations. While several graph-based approaches have the potential to elucidate associations, their effectiveness has not been fully demonstrated. A considerable degree of a priori knowledge, heuristics, and manual filtering is still required. Objectives: In this paper we implement and evaluate a context-driven, automatic subgraph creation method that captures multifaceted complex associations between biomedical concepts to facilitate LBD. Given a pair of concepts, our method automatically generates a ranked list of subgraphs, which provide informative and potentially unknown associations between such concepts. Methods: To generate subgraphs, the set of all MEDLINE articles that contain either of the two specified concepts (A, C) are first collected. Then binary relationships or assertions, which are automatically extracted from the MEDLINE articles, called semantic predications, are used to create a labeled directed predications graph. In this predications graph, a path is represented as a sequence of semantic predica-tions. The hierarchical agglomerative clustering (HAC) algorithm is then applied to cluster paths that are bounded by the two concepts (A, C). HAC relies on implicit semantics captured through Medical Subject Heading (MeSH) descriptors, and explicit semantics from the MeSH hierarchy, for clustering. Paths that exceed a threshold of semantic relatedness are clustered into subgraphs based on their shared context. Finally, the automatically generated clusters are provided as a ranked list of subgraphs. Results: The subgraphs generated using this approach facilitated the rediscovery of 8 out of 9 existing scientific discoveries. In particular, they directly (or indirectly) led to the recovery of several intermediates (or B-concepts) between A-and C-terms, while also providing insights into the meaning of the associations. Such meaning is derived from predicates between the concepts, as well as the provenance of the semantic predications in MEDLINE. Additionally, by generating subgraphs on different thematic dimensions (such as Cellular Activity, Pharmaceutical Treatment and Tissue Function), the approach may enable a broader understanding of the nature of complex associations between concepts. Finally, in a statistical evaluation to determine the interestingness of the subgraphs, it was observed that an arbitrary association is mentioned in only approximately 4 articles in MEDLINE on average. Conclusion: These results suggest that leveraging the implicit and explicit semantics provided by manually assigned MeSH descriptors is an effective representation for capturing the underlying context of complex associations, along multiple thematic dimensions in LBD situations. Published by Elsevier Inc.
Discovering Relations between Indirectly Connected Biomedical Concepts
The complexity and scale of the knowledge in the biomedical domain has motivated research work towards mining heterogeneous data from structured and unstructured knowledge bases. Towards this direction, it is necessary to combine facts in order to formulate hypotheses or draw conclusions about the domain concepts. In this work we attempt to address this problem by using indirect knowledge connecting two concepts in a graph to identify hidden relations between them. The graph represents concepts as vertices and relations as edges, stemming from structured (ontologies) and unstructured (text) data. In this graph we attempt to mine path patterns which potentially characterize a biomedical relation. For our experimental evaluation we focus on two frequent relations, namely "has target", and "may treat". Our results suggest that relation discovery using indirect knowledge is possible, with an AUC that can reach up to 0.8. Finally, analysis of the results indicates tha...
Automated literature mining and hypothesis generation through a network of Medical Subject Headings
ABSTRACTThe scientific literature is vast, growing, and increasingly specialized, making it difficult to connect disparate observations across subfields. To address this problem, we sought to develop automated hypothesis generation by networking at scale the MeSH terms curated by the National Library of Medicine. The result is a Mesh Term Objective Reasoning (MeTeOR) approach that tallies associations among genes, drugs and diseases from PubMed and predicts new ones.Comparisons to reference databases and algorithms show MeTeOR tends to be more reliable. We also show that many predictions based on the literature prior to 2014 were published subsequently. In a practical application, we validated experimentally a surprising new association found by MeTeOR between novel Epidermal Growth Factor Receptor (EGFR) associations and CDK2. We conclude that MeTeOR generates useful hypotheses from the literature (http://meteor.lichtargelab.org/).AUTHOR SUMMARYThe large size and exponential expans...
Proceedings of the 2006 SIAM International Conference on Data Mining, 2006
Two complementary and non-interactive literature sets of articles, when they are considered together, can reveal useful information of scientific interest not apparent in either of the two sets alone. Swanson called the existence of such hidden links as undiscovered public knowledge (UPK). The novel connection between Raynaud disease and fish oils was uncovered from complementary and non-interactive biomedical literature by Swanson in 1986. Since then, there have been many approaches to uncover UPK by mining the biomedical literature. These earlier works, however, required substantial manual intervention to reduce the number of possible connections. This paper proposes a semantic-based mining model for undiscovered public knowledge using the biomedical literature. Our method replaces manual ad-hoc pruning by using semantic knowledge from t he biomedical ontologies. Using the semantic types and semantic relationships of the biomedical concepts, our prototype system can identify the relevant concepts collected from Medline and generate the novel hypothesis between these concepts. The system successfully replicates Swanson's two famous discoveries: Raynaud disease/fish oils and migraine/magnesium. Compared with previous approaches such as LSI-based and traditional association rule-based methods, our method generates much fewer but more relevant novel hypotheses, and requires much less human intervention in the discovery procedure
NETME: on-the-fly knowledge network construction from biomedical literature
Applied Network Science, 2022
Background The rapidly increasing biological literature is a key resource to automatically extract and gain knowledge concerning biological elements and their relations. Knowledge Networks are helpful tools in the context of biological knowledge discovery and modeling. Results We introduce a novel system called NETME, which, starting from a set of full-texts obtained from PubMed, through an easy-to-use web interface, interactively extracts biological elements from ontological databases and then synthesizes a network inferring relations among such elements. The results clearly show that our tool is capable of inferring comprehensive and reliable biological networks.
Integrated Bio-Entity Network: A System for Biological Knowledge Discovery
A significant part of our biological knowledge is centered on relationships between biological entities (bio-entities) such as proteins, genes, small molecules, pathways, gene ontology (GO) terms and diseases. Accumulated at an increasing speed, the information on bio-entity relationships is archived in different forms at scattered places. Most of such information is buried in scientific literature as unstructured text. Organizing heterogeneous information in a structured form not only facilitates study of biological systems using integrative approaches, but also allows discovery of new knowledge in an automatic and systematic way. In this study, we performed a large scale integration of bio-entity relationship information from both databases containing manually annotated, structured information and automatic information extraction of unstructured text in scientific literature. The relationship information we integrated in this study includes protein–protein interactions, protein/gene regulations, protein–small molecule interactions, protein–GO relationships, protein–pathway relationships, and pathway–disease relationships. The relationship information is organized in a graph data structure, named integrated bio-entity network (IBN), where the vertices are the bio-entities and edges represent their relationships. Under this framework, graph theoretic algorithms can be designed to perform various knowledge discovery tasks. We designed breadth-first search with pruning (BFSP) and most probable path (MPP) algorithms to automatically generate hypotheses—the indirect relationships with high probabilities in the network. We show that IBN can be used to generate plausible hypotheses, which not only help to better understand the complex interactions in biological systems, but also provide guidance for experimental designs.
Content-rich biological network constructed by mining PubMed abstracts
The integration of the rapidly expanding corpus of information about the genome, transcriptome, and proteome, engendered by powerful technological advances, such as microarrays, and the availability of genomic sequence from multiple species, challenges the grasp and comprehension of the scientific community. Despite the existence of text-mining methods that identify biological relationships based on the textual co-occurrence of gene/protein terms or similarities in abstract texts, knowledge of the underlying molecular connections on a large scale, which is prerequisite to understanding novel biological processes, lags far behind the accumulation of data. While computationally efficient, the co-occurrence-based approaches fail to characterize (e.g., inhibition or stimulation, directionality) biological interactions. Programs with natural language processing (NLP) capability have been created to address these limitations, however, they are in general not readily accessible to the public.