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

SN 2020bvc : A Broad-line Type Ic Supernova with a Double-peaked Optical Light Curve and a Luminous X-Ray and Radio Counterpart

We present optical, radio, and X-ray observations of SN 2020bvc (=ASASSN-20bs, ZTF 20aalxlis), a nearby (z = 0.0252; d.=.114Mpc) broad-line (BL) Type Ic supernova (SN) and the first double-peaked Ic-BL discovered without a gamma-ray burst (GRB) trigger. Our observations show that SN 2020bvc shares several properties in common with the Ic-BL SN 2006aj, which was associated with the low-luminosity gamma-ray burst (LLGRB) 060218. First, the 10 GHz radio luminosity (L-radio approximate to 10(37) erg s(-1)) is brighter than ordinary core-collapse SNe but fainter than LLGRB SNe such as SN 1998bw (associated with LLGRB 980425). We model our VLA observations (spanning 13-43 days) as synchrotron emission from a mildly relativistic (v greater than or similar to 0.3c) forward shock. Second, with Swift and Chandra, we detect X-ray emission (L-X approximate to 10(41) erg s(-1)) that is not naturally explained as inverse Compton emission or part of the same synchrotron spectrum as the radio emission. Third, high-cadence (6x night(-1)) data from the Zwicky Transient Facility (ZTF) show a double-peaked optical light curve, the first peak from shock cooling of extended low-mass material (mass M-e 10(12) cm) and the second peak from the radioactive decay of 56Ni. SN 2020bvc is the first double-peaked Ic-BL SN discovered without a GRB trigger, so it is noteworthy that it shows X-ray and radio emission similar to LLGRB SNe. For four of the five other nearby (z less than or similar to 0.05) Ic-BL SNe with ZTF high-cadence data, we rule out a first peak like that seen in SN 2006aj and SN 2020bvc, i.e., that lasts approximate to 1 day.and reaches a peak luminosity M approximate to -18. Follow-up X-ray and radio observations of Ic-BL SNe with well-sampled early optical light curves will establish whether double-peaked optical light curves are indeed predictive of LLGRB-like X-ray and radio emission.Peer reviewe

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update

The purpose of this guideline is to provide information for the interpretation of clinical dihydropyrimidine dehydrogenase (DPYD) genotype tests so that the results can be used to guide dosing of fluoropyrimidines (5-fluorouracil and capecitabine). Detailed guidelines for the use of fluoropyrimidines, their clinical pharmacology, as well as analyses of cost-effectiveness are beyond the scope of this document. The Clinical Pharmacogenetics Implementation Consortium (CPIC®) guidelines consider the situation of patients for which genotype data are already available (updates available at https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/)

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update.

The purpose of this guideline is to provide information for the interpretation of clinical dihydropyrimidine dehydrogenase (DPYD) genotype tests so that the results can be used to guide dosing of fluoropyrimidines (5-fluorouracil and capecitabine). Detailed guidelines for the use of fluoropyrimidines, their clinical pharmacology, as well as analyses of cost-effectiveness are beyond the scope of this document. The Clinical Pharmacogenetics Implementation Consortium (CPIC® ) guidelines consider the situation of patients for which genotype data are already available (updates available at https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/)