Angiotensin antagonists are primarily used in the treatment of hypertension, congestive heart failure, and heart attacks

Angiotensin antagonists are primarily used in the treatment of hypertension, congestive heart failure, and heart attacks. traditional antipsychotics, some of which had published literature evidence indicating their treatment benefits in SCZ patients. In summary, although the fundamental pathophysiological mechanisms of SCZ remain unknown, integrated systems approaches to studying phenotypic connections among diseases may facilitate the discovery of innovative SCZ drugs. + is the column-normalized adjacency matrix of PDN, is a preset probability of L-Glutamic acid monosodium salt restarting from the initial seed node (is a vector in which the element holds the normalized ranking score of disease at iteration. The initial probability vector is less than 10?6. 2.2. Analyze disease class distribution at different ranking cutoffs To better understand ranked diseases, we analyzed disease class distribution at ten different ranking cutoffs. Using SCZ as the seed, we retrieved a ranked list of 7204 diseases from PDN. We classified these diseases into sixteen categories using the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD10), a disease classification scheme designated by the World Health Organization (WHO) [38]. The ICD10 includes 22 highest-level disease classes (or chapters) such as Neoplasms and Diseases of the nervous system. We used sixteen chapters GCN5 and excluded the other six non-specific disease classes such as Codes for special purposes and Injury, poisoning and certain other consequences of external causes. Because the terms used in ICD10 may differ from those in PDN, we expanded disease terms in ICD10 to their synonyms through UMLS CUIs. Disease chapters and the numbers of diseases in each chapter are listed in Table L-Glutamic acid monosodium salt 1. Table 1 Sixteen disease chapters (classes) and the number of diseases (synonym expanded) in each chapter. is the number of SCZ-related diseases that are currently approved to treat and is the disease ranking score (output from the network-based disease ranking algorithm). During the experiment, we found that certain drugs were consistently ranked highly for both the real PDN and random PDNs. For example, the drug chlordiazepoxide was ranked at top 0.32% for the real PDN and on average at top 0.36% for andom PDNs. We designed our reprioritization strategy by accounting for rankings of a drug for random PDNs. A drug was ranked highly if and only if it was ranked highly based on the real PDN and the ratio of its ranking for the real PDN L-Glutamic acid monosodium salt to that for random PDNs is at least 2 fold. 2.3.2. Comparison of four TreatKBs in a de-novo validation L-Glutamic acid monosodium salt setting using 18 known SCZ drugs L-Glutamic acid monosodium salt as evaluation dataset In order to systematically reposition drug treatments from one disease to another, it is critical to have a comprehensive drug treatment knowledge base. In our recent studies, we constructed four large-scale drug-disease treatment knowledge bases (TreatKBs) from multiple heterogeneous and complementary data sources using advanced computational techniques including natural language processing, text mining, and data mining [26, 27, 28]. The databases included 9,216 drug-disease treatment pairs extracted from FDA drug labels, 111,862 pairs extracted from the FDA Adverse Event Reporting System (FAERS), a database supporting the FDAs post-marketing drug safety surveillance efforts, 34,306 pairs extracted from 22 million published biomedical literature abstracts, and 69,724 pairs extracted from 171,805 clinical trials. The combined TreatKB consists of 208,330 unique drug-disease treatment pairs, representing 2484 drugs and 24,511 unique disease concepts. We evaluated PhenoPredict using all 18 FDA-approved SCZ drugs by comparing its performance across four TreatKBs. Since SCZ and its associated drug treatment pairs were removed from the inputs to the repositioning algorithm (SCZ-related diseases and drug-disease treatment pairs), the evaluation is in fact a validation. We calculated the rankings of the 18 FDA-approved SCZ drugs among all retrieved drugs and used them as our gold standard. We assumed that the higher these gold standard drugs were ranked, the better the ranking algorithm.

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