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Tyrosine kinase inhibitors (TKIs) are prescribed for chronic myeloid leukemia (CML) and some other cancers. The objective was to predict and rank TKI-related adverse events (AEs), including under-reported or preclinical AEs, using novel text mining. First, k-means clustering of 2575 clinical CML TKI abstracts separated TKIs by significant (p < 0.05) AE type: gastrointestinal (bosutinib); edema (imatinib); pulmonary (dasatinib); diabetes (nilotinib); cardiovascular (ponatinib). Next, we propose a novel cross-domain text mining method utilizing a knowledge graph, link prediction, and hub node network analysis to predict new relationships. Cross-domain text mining of 30+ million articles via SemNet predicted and ranked known and novel TKI AEs. Three physiology-based tiers were formed using unsupervised rank aggregation feature importance. Tier 1 ranked in the top 1%: hematology (anemia, neutropenia, thrombocytopenia, hypocellular marrow); glucose (diabetes, insulin resistance, metabolic syndrome); iron (deficiency, overload, metabolism), cardiovascular (hypertension, heart failure, vascular dilation); thyroid (hypothyroidism, hyperthyroidism, parathyroid). Tier 2 ranked in the top 5%: inflammation (chronic inflammatory disorder, autoimmune, periodontitis); kidney (glomerulonephritis, glomerulopathy, toxic nephropathy). Tier 3 ranked in the top 10%: gastrointestinal (bowel regulation, hepatitis, pancreatitis); neuromuscular (autonomia, neuropathy, muscle pain); others (secondary cancers, vitamin deficiency, edema). Results suggest proactive TKI patient AE surveillance levels: regular surveillance for tier 1, infrequent surveillance for tier 2, and symptom-based surveillance for tier 3.
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Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease
Parkinson’s disease (PD) is a movement disorder caused by a dopamine deficit in the brain. Current therapies primarily focus on dopamine modulators or replacements, such as levodopa. Although dopamine replacement can help alleviate PD symptoms, therapies targeting the underlying neurodegenerative process are limited. The study objective was to use artificial intelligence to rank the most promising repurposed drug candidates for PD. Natural language processing (NLP) techniques were used to extract text relationships from 33+ million biomedical journal articles from PubMed and map relationships between genes, proteins, drugs, diseases, etc., into a knowledge graph. Cross-domain text mining, hub network analysis, and unsupervised learning rank aggregation were performed in SemNet 2.0 to predict the most relevant drug candidates to levodopa and PD using relevance-based HeteSim scores. The top predicted adjuvant PD therapies included ebastine, an antihistamine for perennial allergic rhinitis; levocetirizine, another antihistamine; vancomycin, a powerful antibiotic; captopril, an angiotensin-converting enzyme (ACE) inhibitor; and neramexane, an N-methyl-D-aspartate (NMDA) receptor agonist. Cross-domain text mining predicted that antihistamines exhibit the capacity to synergistically alleviate Parkinsonian symptoms when used with dopamine modulators like levodopa or levodopa–carbidopa. The relationship patterns among the identified adjuvant candidates suggest that the likely therapeutic mechanism(s) of action of antihistamines for combatting the multi-factorial PD pathology include counteracting oxidative stress, amending the balance of neurotransmitters, and decreasing the proliferation of inflammatory mediators. Finally, cross-domain text mining interestingly predicted a strong relationship between PD and liver disease.
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- Award ID(s):
- 1944247
- PAR ID:
- 10502321
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- International Journal of Molecular Sciences
- Volume:
- 24
- Issue:
- 15
- ISSN:
- 1422-0067
- Page Range / eLocation ID:
- 12339
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/ijms241512339
