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Identifying and Validating Networks of Oncology Biomarkers Mined From the Scientific Literature.

ABSTRACT: Biomarkers, as measurements of defined biological characteristics, can play a pivotal role in estimations of disease risk, early detection, differential diagnosis, assessment of disease progression and outcomes prediction. Studies of cancer biomarkers are published daily; some are well characterized, while others are of growing interest. Managing this flow of information is challenging for scientists and clinicians. We sought to develop a novel text-mining method employing biomarker co-occurrence processing applied to a deeply indexed full-text database to generate time-interval-delimited biomarker co-occurrence networks. Biomarkers across 6 cancer sites and a cancer-agnostic network were successfully characterized in terms of their emergence in the published literature and the context in which they are described. Our approach, which enables us to find publications based on biomarker relationships, identified biomarker relationships not known to existing interaction networks. This search method finds relevant literature that could be missed with keyword searches, even if full text is available. It enables users to extract relevant biological information and may provide new biological insights that could not be achieved by individual review of papers.

SUBMITTER: Wager K

PROVIDER: S-EPMC8943609 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Identifying and Validating Networks of Oncology Biomarkers Mined From the Scientific Literature.

Wager Kim K Chari Dheepa D Ho Steffan S Rees Tomas T Penner Orion O Schijvenaars Bob Ja BJ

Cancer informatics 20220322

Biomarkers, as measurements of defined biological characteristics, can play a pivotal role in estimations of disease risk, early detection, differential diagnosis, assessment of disease progression and outcomes prediction. Studies of cancer biomarkers are published daily; some are well characterized, while others are of growing interest. Managing this flow of information is challenging for scientists and clinicians. We sought to develop a novel text-mining method employing biomarker co-occurrenc ...[more]

PMID: 35342286

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Project description:INTRODUCTION:Given that adverse drug effects (ADEs) have led to post-market patient harm and subsequent drug withdrawal, failure of candidate agents in the drug development process, and other negative outcomes, it is essential to attempt to forecast ADEs and other relevant drug-target-effect relationships as early as possible. Current pharmacologic data sources, providing multiple complementary perspectives on the drug-target-effect paradigm, can be integrated to facilitate the inference of relationships between these entities. OBJECTIVE:This study aims to identify both existing and unknown relationships between chemicals (C), protein targets (T), and ADEs (E) based on evidence in the literature. MATERIALS AND METHODS:Cheminformatics and data mining approaches were employed to integrate and analyze publicly available clinical pharmacology data and literature assertions interrelating drugs, targets, and ADEs. Based on these assertions, a C-T-E relationship knowledge base was developed. Known pairwise relationships between chemicals, targets, and ADEs were collected from several pharmacological and biomedical data sources. These relationships were curated and integrated according to Swanson's paradigm to form C-T-E triangles. Missing C-E edges were then inferred as C-E relationships. RESULTS:Unreported associations between drugs, targets, and ADEs were inferred, and inferences were prioritized as testable hypotheses. Several C-E inferences, including testosterone → myocardial infarction, were identified using inferences based on the literature sources published prior to confirmatory case reports. Timestamping approaches confirmed the predictive ability of this inference strategy on a larger scale. CONCLUSIONS:The presented workflow, based on free-access databases and an association-based inference scheme, provided novel C-E relationships that have been validated post hoc in case reports. With refinement of prioritization schemes for the generated C-E inferences, this workflow may provide an effective computational method for the early detection of potential drug candidate ADEs that can be followed by targeted experimental investigations.

Project description:BackgroundWe obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins), comparative proteomic data (56 differentially expressed proteins), and nitroproteomic data (17 nitroproteins). There is a pressing need to clarify the significant signaling pathway networks that derive from those proteins in order to clarify and to better understand the molecular basis of pituitary adenoma pathogenesis and to discover biomarkers. Here, we describe the significant signaling pathway networks that were mined from human pituitary adenoma proteomic data with the Ingenuity pathway analysis system.MethodsThe Ingenuity pathway analysis system was used to analyze signal pathway networks and canonical pathways from protein-mapping data, comparative proteomic data, adenoma nitroproteomic data, and control nitroproteomic data. A Fisher's exact test was used to test the statistical significance with a significance level of 0.05. Statistical significant results were rationalized within the pituitary adenoma biological system with literature-based bioinformatics analyses.ResultsFor the protein-mapping data, the top pathway networks were related to cancer, cell death, and lipid metabolism; the top canonical toxicity pathways included acute-phase response, oxidative-stress response, oxidative stress, and cell-cycle G2/M transition regulation. For the comparative proteomic data, top pathway networks were related to cancer, endocrine system development and function, and lipid metabolism; the top canonical toxicity pathways included mitochondrial dysfunction, oxidative phosphorylation, oxidative-stress response, and ERK/MAPK signaling. The nitroproteomic data from a pituitary adenoma were related to cancer, cell death, lipid metabolism, and reproductive system disease, and the top canonical toxicity pathways mainly related to p38 MAPK signaling and cell-cycle G2/M transition regulation. Nitroproteins from a pituitary control related to gene expression and cellular development, and no canonical toxicity pathways were identified.ConclusionsThis pathway network analysis demonstrated that mitochondrial dysfunction, oxidative stress, cell-cycle dysregulation, and the MAPK-signaling abnormality are significantly associated with a pituitary adenoma. These pathway-network data provide new insights into the molecular mechanisms of human pituitary adenoma pathogenesis, and new clues for an in-depth investigation of pituitary adenoma and biomarker discovery.

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Identifying and Validating Networks of Oncology Biomarkers Mined From the Scientific Literature.

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Identifying and Validating Networks of Oncology Biomarkers Mined From the Scientific Literature.

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