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Blockade of hERG channels may cause prolonged QT intervals that potentially could lead to cardiotoxicity. Various in-silico techniques including deep learning models are widely used to screen out small molecules with potential hERG related toxicity. Most of the published deep learning methods utilize a single type of features which might restrict their performance. Methods based on more than one type of features such as DeepHIT struggle with the aggregation of extracted information. DeepHIT shows better performance when evaluated against one or two accuracy metrics such as negative predictive value (NPV) and sensitivity (SEN) but struggle when evaluated against others such as Matthew correlation coefficient (MCC), accuracy (ACC), positive predictive value (PPV) and specificity (SPE). Therefore, there is a need for a method that can efficiently aggregate information gathered from models based on different chemical representations and boost hERG toxicity prediction over a range of performance metrics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this paper, we propose a deep learning framework based on step-wise training to predict hERG channel blocking activity of small molecules. Our approach utilizes five individual deep learning base models with their respective base features and a separate neural network to combine the outputs of the five base models. By using three external independent test sets with potency activity of IC<jats:sub>50<\/jats:sub>at a threshold of 10<jats:inline-formula><jats:alternatives><jats:tex-math>$$\\upmu$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mi>\u03bc<\/mml:mi><\/mml:math><\/jats:alternatives><\/jats:inline-formula>m, our method achieves better performance for a combination of classification metrics. We also investigate the effective aggregation of chemical information extracted for robust hERG activity prediction. In summary, CardioTox net can serve as a robust tool for screening small molecules for hERG channel blockade in drug discovery pipelines and performs better than previously reported methods on a range of classification metrics.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13321-021-00541-z","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T09:04:23Z","timestamp":1629104663000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["CardioTox net: a robust predictor for hERG channel blockade based on deep learning meta-feature ensembles"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4431-7507","authenticated-orcid":false,"given":"Abdul","family":"Karim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Balle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-2052","authenticated-orcid":false,"given":"Abdul","family":"Sattar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"issue":"2","key":"541_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.4161\/chan.2.2.6004","volume":"2","author":"B Priest","year":"2008","unstructured":"Priest B, Bell IM, Garcia M (2008) Role of herg potassium channel assays in drug development. 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