PGxMine: Text Mining for Curation of PharmGKB

Precision medicine tailors treatment to individuals personal data including differences in their genome. The Pharmacogenomics Knowledgebase (PharmGKB) provides highly curated information on the effect of genetic variation on drug response and side effects for a wide range of drugs. PharmGKB's scientific curators triage, review and annotate a large number of papers each year but the task is challenging. We present the PGxMine resource, a text-mined resource of pharmacogenomic associations from all accessible published literature to assist in the curation of PharmGKB. We developed a supervised machine learning pipeline to extract associations between a variant (DNA and protein changes, star alleles and dbSNP identifiers) and a chemical. PGxMine covers 452 chemicals and 2,426 variants and contains 19,930 mentions of pharmacogenomic associations across 7,170 papers. An evaluation by PharmGKB curators found that 57 of the top 100 associations not found in PharmGKB led to 83 curatable papers and a further 24 associations would likely lead to curatable papers through citations. The results can be viewed at https://pgxmine.pharmgkb.org/ and code can be downloaded at https://github.com/jakelever/pgxmine

Text-mining clinically relevant cancer biomarkers for curation into the CIViC database

Background: Precision oncology involves analysis of individual cancer samples to understand the genes and pathways involved in the development and progression of a cancer. To improve patient care, knowledge of diagnostic, prognostic, predisposing, and drug response markers is essential. Several knowledgebases have been created by different groups to collate evidence for these associations. These include the open-access Clinical Interpretation of Variants in Cancer (CIViC) knowledgebase. These databases rely on time-consuming manual curation from skilled experts who read and interpret the relevant biomedical literature. Methods: To aid in this curation and provide the greatest coverage for these databases, particularly CIViC, we propose the use of text mining approaches to extract these clinically relevant biomarkers from all available published literature. To this end, a group of cancer genomics experts annotated sentences that discussed biomarkers with their clinical associations and achieved good inter-annotator agreement. We then used a supervised learning approach to construct the CIViCmine knowledgebase. Results: We extracted 121,589 relevant sentences from PubMed abstracts and PubMed Central Open Access full-text papers. CIViCmine contains over 87,412 biomarkers associated with 8035 genes, 337 drugs, and 572 cancer types, representing 25,818 abstracts and 39,795 full-text publications. Conclusions: Through integration with CIVIC, we provide a prioritized list of curatable clinically relevant cancer biomarkers as well as a resource that is valuable to other knowledgebases and precision cancer analysts in general. All data is publically available and distributed with a Creative Commons Zero license. The CIViCmine knowledgebase is available at http://bionlp.bcgsc.ca/civicmine/

Distribution of \u3cem\u3eMycobacterium ulcerans\u3c/em\u3e in Aquatic Environments in Ghana

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a necrotizing skin disease prevalent in 30 countries of West Africa and Australia. The disease begins as a painless nodule or papule that, if left untreated, can lead to ulceration that can cover much of the body. Though not usually fatal, morbidity is high, especially in rural areas where the disease is prevalent. Epidemiological evidence has linked incidence of Buruli ulcer to slow moving or stagnant waters, but despite this, the mode of transmission is not known. Evidence for M. ulcerans in aquatic environments has relied on detection based upon PCR targeting IS2404, an insertion sequence once thought to be specific for M. ulcerans. In the past few years a growing body of evidence has shown IS2404 present in a number of aquatic mycobacterial species. Although the use of PCR primers targeting the mycolactone toxin has increased the sensitivity of M. ulcerans PCR, many ulcerans-like mycobacteria also contain the mycolactone genes. In the studies presented in this body of work we applied variable number of tandem repeat (VNTR) typing methods to environmental samples in order to map the distribution of M. ulcerans in aquatic environments in Ghana both endemic and non-endemic for Buruli ulcer. Environmental samples were collected using standardized ecological methods of sampling from 2004 until 2007. VNTR profiling was also used to genotype tissue samples of patients with Buruli ulcer in an effort to link environmental samples to human cases. Finally, the ability of M. ulcerans to associate and survive within amoeba was also tested. Results from this work demonstrate the presence of M. ulcerans in both endemic and nonendemic aquatic environments in Ghana and the association with protists. Considerable M. ulcerans heterogeneity was also found between patient and environmental samples. Results also support the use of VNTR profiling for confirmation of M. ulcerans in environmental samples, and for molecular epidemiology

Las Vegas Morning Gazette, 09-21-1880

https://digitalrepository.unm.edu/lv_gazette_news/2399/thumbnail.jp

Slow transit constipation: clinical and aetiological studies.

PhDConstipation is the second most commonly self-reported gastrointestinal symptom. On the basis of anorectal physiological investigations and colonic transit studies, a subgroup of patients with several intractable symptoms, but without organic disease will be found to have slow transit constipation (STC). STC is a condition of gut dysmotility which predominantly affects young women, and may result in surgical intervention with variable, often unsatisfactory results. The aetiology remains elusive. New aetiological hypotheses for STC were examined following full clinical and pathophysiological characterisation of a large cohort of 130 patients referred to our institution over the last 10 years. Aspects of nerve and muscle dysfunction were studied. A new scoring system demonstrated some ability of multiple symptoms to discriminate STC from other forms of constipation. Detailed clinical and gastrointestinal physiological studies confirmed the heterogeneity of STC patients. Some significant physiological differences were detectable between clinically defined sub-groups of patients and refuted previous assumptions based on smaller numbers. Detailed neurophysiological studies, including quantitative peripheral sensory and autonomic testing, provided evidence of a small fibre neuropathy in a proportion of patients with STC. Mutational screening of some early-onset cases for a possible congenital pathogenetic mechanism, based on the observation that some STC patients had relatives with Hirschsprung's disease demonstrated that mutation of 2 important genes now implicated in this disorder were not a frequent cause of STC. Serum immunoprecipitation assays showed that anti-neuronal ion channel autoantibodies may have an as yet unrecognised role in the development of STC in a small proportion of acquired cases. An inclusion body myopathy was identifiable in colonic tissue of patients with STC, and this appeared to arise secondary to denervation. Further knowledge of the single or multiple pathogenetic mechanisms leading to this clinical condition may allow more rational or directed therapies aimed at the correction of the disease process or processes themselves