BackgroundDrug ontologies could help pharmaceutical researchers overcome information overload and speed the pace of drug discovery, thus benefiting the industry and patients alike. Drug-disease relations, specifically drug-indication relations, are a prime candidate for representation in ontologies. There is a wealth of available drug-indication information, but structuring and integrating it is challenging.ResultsWe created a drug-indication database (DID) of data from 12 openly available, commercially available, and proprietary information sources, integrated by terminological normalization to UMLS and other authorities. Across sources, there are 29,964 unique raw drug/chemical names, 10,938 unique raw indication ”target” terms, and 192,008 unique raw drug-indication pairs. Drug/chemical name normalization to CAS numbers or UMLS concepts reduced the unique name count to 91 or 85% of the raw count, respectively, 84% if combined. Indication ”target” normalization to UMLS ”phenotypic-type” concepts reduced the unique term count to 57% of the raw count. The 12 sources of raw data varied widely in coverage (numbers of unique drug/chemical and indication concepts and relations) generally consistent with the idiosyncrasies of each source, but had strikingly little overlap, suggesting that we successfully achieved source/raw data diversity.ConclusionsThe DID is a database of structured drug-indication relations intended to facilitate building practical, comprehensive, integrated drug ontologies. The DID itself is not an ontology, but could be converted to one more easily than the contributing raw data. Our methodology could be adapted to the creation of other structured drug-disease databases such as for contraindications, precautions, warnings, and side effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s13326-016-0110-0) contains supplementary material, which is available to authorized users.
We radioiodinated a synthetic fragment representing residues 44-68 from the middle region of human parathyroid hormone (hPTH). At least 90% of the purified [125I]-hPTH-(44-68) was able to bind to anti-hPTH serum. Antibody-bound [125I]hPTH-(44-68) could be rapidly and efficiently separated from nonbound radioligand by dextran-coated charcoal. [125I]hPTH-(44-68) was not degraded after a 72-h incubation in undiluted plasma at 7 C, and it was stable for many weeks at -20 C in a 1% albumin buffer. [125I]hPTH-(44-68) was used to develop midregion specific PTH RIAs. The immunoreactive PTH concentration in plasma was above the upper limit of the normal range in 39 of 43 patients with primary hyperparathyroidism. Values from the midregion assay and an established carboxy-terminus assay correlated using peripheral plasma from 17 patients with primary hyperparathyroidism (r = 0.84; P less than 0.0001) or using parathyroid gland venous effluent plasma from the same 17 patients (r = 0.79; P less than 0.0005). Gel filtration analysis of peripheral plasma from 2 patients with primary hyperparathyroidism and azotemia suggested peptides possessing midregion immunoreactivity but deficient in carboxyterminus immunoreactivity. Similar peptides were present at higher concentrations in parathyroid gland venous effluent plasma than in peripheral plasma, indicating release from the parathyroid gland. In conclusion, [125I]hPTH-(44-68) had properties favorable for the development of RIAs reactive solely with the midregion of PTH. Fragments secreted in vivo by two human parathyroid glands were reactive in midregion assays but nonreactive in a carboxy-terminus assay.
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