RESUMEN
Recently, drug toxicity has become a critical problem with heavy medical and economic burdens. Acquired long QT syndrome (acLQTS) is an acquired cardiac ion channel disease caused by drugs blocking the hERG channel. Therefore, it is necessary to avoid cardiotoxicity in drug design, and computer models have been widely used to fix this predicament. In this study, we collected a hERG inhibitor dataset containing 8671 compounds, and then, these compounds were featurized by traditional molecular fingerprints (including Baseline2D, ECFP4, PropertyFP, and 3DFP) and the newly proposed molecular dynamics fingerprint (MDFP). Subsequently, regression prediction models were established by using four machine learning algorithms based on these fingerprints and the combined multi-dimensional molecular fingerprints (MultiFP). After cross-validation and independent test dataset validation, the results show that the best model was built by the consensus of four algorithms with MultiFP, and this model bests recently published methods in terms of hERG cardiotoxicity prediction with a RMSE of 0.531 and a R2 of 0.653 on the test dataset. Feature importance analysis and correlation analysis identified some novel structural features and molecular dynamics features that are highly associated with the hERG inhibition of compounds. Our findings provide new insight into multi-dimensional molecular fingerprints and consensus models for hERG cardiotoxicity prediction.
Asunto(s)
Canales de Potasio Éter-A-Go-Go , Bloqueadores de los Canales de Potasio , Cardiotoxicidad , Canales de Potasio Éter-A-Go-Go/química , Canales de Potasio Éter-A-Go-Go/metabolismo , Humanos , Aprendizaje Automático , Simulación de Dinámica Molecular , Bloqueadores de los Canales de Potasio/química , Bloqueadores de los Canales de Potasio/farmacologíaRESUMEN
Newman and Cain (Newman, Cain 2014 Psychol. Sci. 25, 648-655 (doi:10.1177/0956797613504785)) reported that observers view a person's choices as less ethical when that person has acted in response to both altruistic and selfish (commercial) motivations, as compared with purely selfish interests. The altruistic component reduces the observers' approval rather than raising it. This puzzling phenomenon termed the 'tainted altruism' effect, has attracted considerable interest but no direct replications in prior research. We report direct replications of Newman and Cain's Experiments 2 and 3, using a larger sample (n = 501) intended to be fairly representative of the US population. The results confirm the original findings in considerable detail.
RESUMEN
Clinical cases of chromosome 7 long-arm end deletion are rare. Generally, 7q terminal deletion syndrome results in complex clinical phenotypes, such as microcephaly, growth and development retardation, holoprosencephaly, and sacral hypoplasia. Herein, we report the genetic and clinical features of a fetus with multiple malformations observed by prenatal ultrasound. The results showed that there was a large fragment deletion of approximately 27.7 Mb in 7q32.3-qter. The induced fetus showed facial abnormalities of cleft lip and palate, and some organ structural abnormalities (such as diaphragmatic hernia and polycystic renal dysplasia) were observed by autopsy and pathology. To provide more reliable information for disease diagnosis and genetic counseling, we reviewed and analyzed the reported cases of isolated 7q terminal syndrome.