Abstract：
:Gain-of-function mutations in human androgen receptor (AR) are among the major causes of drug resistance in prostate cancer (PCa). Identifying mutations that cause resistant phenotype is of critical importance for guiding treatment protocols, as well as for designing drugs that do not elicit adverse responses. However, experimental characterization of these mutations is time consuming and costly; thus, predictive models are needed to anticipate resistant mutations and to guide the drug discovery process. In this work, we leverage experimental data collected on 68 AR mutants, either observed in the clinic or described in the literature, to train a deep neural network (DNN) that predicts the response of these mutants to currently used and experimental anti-androgens and testosterone. We demonstrate that the use of this DNN, with general 2D descriptors, provides a more accurate prediction of the biological outcome (inhibition, activation, no-response, mixed-response) in AR mutant-drug pairs compared to other machine learning approaches. Finally, the developed approach was used to make predictions of AR mutant response to the latest AR inhibitor darolutamide, which were then validated by in-vitro experiments.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Snow O,Lallous N,Ester M,Cherkasov Adoi
10.3390/ijms21165847subject
Has Abstractpub_date
2020-08-14 00:00:00issue
16issn
1422-0067pii
ijms21165847journal_volume
21pub_type
杂志文章abstract：:The effects of acidic polysaccharides purified from Gastrodia rhizome on blood pressure and serum lipid levels in spontaneously hypertensive rats (SHR) fed a high-fat diet were investigated. Acidic polysaccharides were purified from crude polysaccharides by DEAE-Sepharose CL-6B. Thirty-six male SHR were randomly divid...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms13010698
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18010108
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms17101673
更新日期：2016-10-02 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18040870
更新日期：2017-04-20 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2019-05-09 00:00:00
abstract：:Gap junction-mediated intercellular communication facilitates the circulation of ions, small molecules, and metabolites in the avascular eye lens. Mutants of the lens fiber cell gap junction proteins, connexin46 (Cx46) and connexin50 (Cx50), cause cataracts in people and in mice. Studies in mouse models have begun to ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19010126
更新日期：2018-01-02 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20030732
更新日期：2019-02-09 00:00:00
abstract：:That the nervous system is the main target of lead (Pb) has long been considered an established fact until recent evidence has linked the Pb effect on the immune system to the toxic effects of Pb on the nervous system. In this paper, we present recent literature reports on the effect of Pb on the inflammatory processe...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2016-12-19 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21072340
更新日期：2020-03-28 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21114188
更新日期：2020-06-11 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18061245
更新日期：2017-06-10 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21239138
更新日期：2020-11-30 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 社论
doi：10.3390/ijms20163879
更新日期：2019-08-09 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20051078
更新日期：2019-03-02 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21249426
更新日期：2020-12-10 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20215269
更新日期：2019-10-24 00:00:00
abstract：:Articular cartilage (AC) is an avascular tissue composed of scattered chondrocytes embedded in a dense extracellular matrix, in which nourishment takes place via the synovial fluid at the surface. AC has a limited intrinsic healing capacity, and thus mainly surgical techniques have been used to relieve pain and improv...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21218249
更新日期：2020-11-04 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19071866
更新日期：2018-06-25 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21155574
更新日期：2020-08-04 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms22020731
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18020342
更新日期：2017-02-07 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21144880
更新日期：2020-07-10 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2011-01-01 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2017-08-01 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-07-11 00:00:00
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journal_title：International journal of molecular sciences
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doi：10.3390/ijms20225735
更新日期：2019-11-15 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2018-07-06 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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abstract：:C-type lectin receptors and their adaptor molecules are involved in the recognition of glycosylated self-antigens and pathogens. However, little is known about the species- and organ-specific expression profiles of these molecules. We therefore determined the mRNA expression levels of Dectin-1, MR1, MR2, DC-SIGN, Syk,...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms130810113
更新日期：2012-01-01 00:00:00
