DTox: A deep neural network-based in visio lens for large scale toxicogenomics data
J Toxicol Sci. 2024;49(3):105-115. doi: 10.2131/jts.49.105.ABSTRACTWith the advancement of large-scale omics technologies, particularly transcriptomics data sets on drug and treatment response repositories available in public domain, toxicogenomics has emerged as a key field in safety pharmacology and chemical risk assessment. Traditional statistics-based bioinformatics analysis poses challenges in its application across multidimensional toxicogenomic data, including administration time, dosage, and gene expression levels. Motivated by the visual inspection workflow of field experts to augment their efficiency of screening...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Takeshi Hase Samik Ghosh Ken-Ichi Aisaki Satoshi Kitajima Jun Kanno Hiroaki Kitano Ayako Yachie Source Type: research
Developing a GNN-based AI model to predict mitochondrial toxicity using the bagging method
J Toxicol Sci. 2024;49(3):117-126. doi: 10.2131/jts.49.117.ABSTRACTMitochondrial toxicity has been implicated in the development of various toxicities, including hepatotoxicity. Therefore, mitochondrial toxicity has become a major screening factor in the early discovery phase of drug development. Several models have been developed to predict mitochondrial toxicity based on chemical structures. However, they only provide a binary classification of positive or negative results and do not provide the substructures that contribute to a positive decision. Therefore, we developed an artificial intelligence (AI) model to predict ...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Yoshinobu Igarashi Ryosuke Kojima Shigeyuki Matsumoto Hiroaki Iwata Yasushi Okuno Hiroshi Yamada Source Type: research
Discovery and development of COVID-19 vaccines and therapeutics: nonclinical perspectives
J Toxicol Sci. 2024;49(3):79-94. doi: 10.2131/jts.49.79.ABSTRACTThe development and regulatory review of BNT162b2, a COVID-19 vaccine, and PaxlovidTM (nirmatrelvir tablets/ritonavir tablets), a COVID-19 therapeutic, are benchmarks for accelerated innovation during a global pandemic. Rapid choice of the SARS-CoV-2 spike protein and main protease (Mpro) as targets for the vaccine and therapeutic, respectively, leveraged the available knowledge of the biology of SARS-CoV-2 and related viruses. The nonclinical immunogenicity and safety of BNT162b2 was rigorously assessed. Likewise, a comprehensive nonclinical safety assessment...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Nasir Khan Jean Sathish Cynthia M Rohde Source Type: research
Possible nonimmunological toxicological mechanisms of vesnarinone-associated agranulocytosis in HL-60 cells: role of reduced glutathione as cytotoxic defense
In conclusion, we present the first demonstration of the cytotoxic effects and ROS production resulting from the MPO/H2O2/Cl- metabolic reaction of vesnarinone and newly identified the causative metabolite, M2, as the N-chloramine metabolite of M1, which induces cytotoxicity in HL-60 cells. Moreover, a protective role of GSH against the cytotoxicity was revealed. These findings suggest a possible nonimmunological cause of vesnarinone agranulocytosis.PMID:38432956 | DOI:10.2131/jts.49.95 (Source: Journal of Toxicological Sciences)
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Toshihisa Koga Yuko Sahara Tadaaki Ohtani Kaneko Yosuke Ken Umehara Source Type: research
DTox: A deep neural network-based in visio lens for large scale toxicogenomics data
J Toxicol Sci. 2024;49(3):105-115. doi: 10.2131/jts.49.105.ABSTRACTWith the advancement of large-scale omics technologies, particularly transcriptomics data sets on drug and treatment response repositories available in public domain, toxicogenomics has emerged as a key field in safety pharmacology and chemical risk assessment. Traditional statistics-based bioinformatics analysis poses challenges in its application across multidimensional toxicogenomic data, including administration time, dosage, and gene expression levels. Motivated by the visual inspection workflow of field experts to augment their efficiency of screening...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Takeshi Hase Samik Ghosh Ken-Ichi Aisaki Satoshi Kitajima Jun Kanno Hiroaki Kitano Ayako Yachie Source Type: research
Developing a GNN-based AI model to predict mitochondrial toxicity using the bagging method
J Toxicol Sci. 2024;49(3):117-126. doi: 10.2131/jts.49.117.ABSTRACTMitochondrial toxicity has been implicated in the development of various toxicities, including hepatotoxicity. Therefore, mitochondrial toxicity has become a major screening factor in the early discovery phase of drug development. Several models have been developed to predict mitochondrial toxicity based on chemical structures. However, they only provide a binary classification of positive or negative results and do not provide the substructures that contribute to a positive decision. Therefore, we developed an artificial intelligence (AI) model to predict ...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Yoshinobu Igarashi Ryosuke Kojima Shigeyuki Matsumoto Hiroaki Iwata Yasushi Okuno Hiroshi Yamada Source Type: research
Discovery and development of COVID-19 vaccines and therapeutics: nonclinical perspectives
J Toxicol Sci. 2024;49(3):79-94. doi: 10.2131/jts.49.79.ABSTRACTThe development and regulatory review of BNT162b2, a COVID-19 vaccine, and PaxlovidTM (nirmatrelvir tablets/ritonavir tablets), a COVID-19 therapeutic, are benchmarks for accelerated innovation during a global pandemic. Rapid choice of the SARS-CoV-2 spike protein and main protease (Mpro) as targets for the vaccine and therapeutic, respectively, leveraged the available knowledge of the biology of SARS-CoV-2 and related viruses. The nonclinical immunogenicity and safety of BNT162b2 was rigorously assessed. Likewise, a comprehensive nonclinical safety assessment...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Nasir Khan Jean Sathish Cynthia M Rohde Source Type: research
Possible nonimmunological toxicological mechanisms of vesnarinone-associated agranulocytosis in HL-60 cells: role of reduced glutathione as cytotoxic defense
In conclusion, we present the first demonstration of the cytotoxic effects and ROS production resulting from the MPO/H2O2/Cl- metabolic reaction of vesnarinone and newly identified the causative metabolite, M2, as the N-chloramine metabolite of M1, which induces cytotoxicity in HL-60 cells. Moreover, a protective role of GSH against the cytotoxicity was revealed. These findings suggest a possible nonimmunological cause of vesnarinone agranulocytosis.PMID:38432956 | DOI:10.2131/jts.49.95 (Source: Journal of Toxicological Sciences)
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Toshihisa Koga Yuko Sahara Tadaaki Ohtani Kaneko Yosuke Ken Umehara Source Type: research
DTox: A deep neural network-based in visio lens for large scale toxicogenomics data
J Toxicol Sci. 2024;49(3):105-115. doi: 10.2131/jts.49.105.ABSTRACTWith the advancement of large-scale omics technologies, particularly transcriptomics data sets on drug and treatment response repositories available in public domain, toxicogenomics has emerged as a key field in safety pharmacology and chemical risk assessment. Traditional statistics-based bioinformatics analysis poses challenges in its application across multidimensional toxicogenomic data, including administration time, dosage, and gene expression levels. Motivated by the visual inspection workflow of field experts to augment their efficiency of screening...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Takeshi Hase Samik Ghosh Ken-Ichi Aisaki Satoshi Kitajima Jun Kanno Hiroaki Kitano Ayako Yachie Source Type: research
Developing a GNN-based AI model to predict mitochondrial toxicity using the bagging method
J Toxicol Sci. 2024;49(3):117-126. doi: 10.2131/jts.49.117.ABSTRACTMitochondrial toxicity has been implicated in the development of various toxicities, including hepatotoxicity. Therefore, mitochondrial toxicity has become a major screening factor in the early discovery phase of drug development. Several models have been developed to predict mitochondrial toxicity based on chemical structures. However, they only provide a binary classification of positive or negative results and do not provide the substructures that contribute to a positive decision. Therefore, we developed an artificial intelligence (AI) model to predict ...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Yoshinobu Igarashi Ryosuke Kojima Shigeyuki Matsumoto Hiroaki Iwata Yasushi Okuno Hiroshi Yamada Source Type: research
Discovery and development of COVID-19 vaccines and therapeutics: nonclinical perspectives
J Toxicol Sci. 2024;49(3):79-94. doi: 10.2131/jts.49.79.ABSTRACTThe development and regulatory review of BNT162b2, a COVID-19 vaccine, and PaxlovidTM (nirmatrelvir tablets/ritonavir tablets), a COVID-19 therapeutic, are benchmarks for accelerated innovation during a global pandemic. Rapid choice of the SARS-CoV-2 spike protein and main protease (Mpro) as targets for the vaccine and therapeutic, respectively, leveraged the available knowledge of the biology of SARS-CoV-2 and related viruses. The nonclinical immunogenicity and safety of BNT162b2 was rigorously assessed. Likewise, a comprehensive nonclinical safety assessment...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Nasir Khan Jean Sathish Cynthia M Rohde Source Type: research
Possible nonimmunological toxicological mechanisms of vesnarinone-associated agranulocytosis in HL-60 cells: role of reduced glutathione as cytotoxic defense
In conclusion, we present the first demonstration of the cytotoxic effects and ROS production resulting from the MPO/H2O2/Cl- metabolic reaction of vesnarinone and newly identified the causative metabolite, M2, as the N-chloramine metabolite of M1, which induces cytotoxicity in HL-60 cells. Moreover, a protective role of GSH against the cytotoxicity was revealed. These findings suggest a possible nonimmunological cause of vesnarinone agranulocytosis.PMID:38432956 | DOI:10.2131/jts.49.95 (Source: Journal of Toxicological Sciences)
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Toshihisa Koga Yuko Sahara Tadaaki Ohtani Kaneko Yosuke Ken Umehara Source Type: research
DTox: A deep neural network-based in visio lens for large scale toxicogenomics data
J Toxicol Sci. 2024;49(3):105-115. doi: 10.2131/jts.49.105.ABSTRACTWith the advancement of large-scale omics technologies, particularly transcriptomics data sets on drug and treatment response repositories available in public domain, toxicogenomics has emerged as a key field in safety pharmacology and chemical risk assessment. Traditional statistics-based bioinformatics analysis poses challenges in its application across multidimensional toxicogenomic data, including administration time, dosage, and gene expression levels. Motivated by the visual inspection workflow of field experts to augment their efficiency of screening...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Takeshi Hase Samik Ghosh Ken-Ichi Aisaki Satoshi Kitajima Jun Kanno Hiroaki Kitano Ayako Yachie Source Type: research
Developing a GNN-based AI model to predict mitochondrial toxicity using the bagging method
J Toxicol Sci. 2024;49(3):117-126. doi: 10.2131/jts.49.117.ABSTRACTMitochondrial toxicity has been implicated in the development of various toxicities, including hepatotoxicity. Therefore, mitochondrial toxicity has become a major screening factor in the early discovery phase of drug development. Several models have been developed to predict mitochondrial toxicity based on chemical structures. However, they only provide a binary classification of positive or negative results and do not provide the substructures that contribute to a positive decision. Therefore, we developed an artificial intelligence (AI) model to predict ...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Yoshinobu Igarashi Ryosuke Kojima Shigeyuki Matsumoto Hiroaki Iwata Yasushi Okuno Hiroshi Yamada Source Type: research
Discovery and development of COVID-19 vaccines and therapeutics: nonclinical perspectives
J Toxicol Sci. 2024;49(3):79-94. doi: 10.2131/jts.49.79.ABSTRACTThe development and regulatory review of BNT162b2, a COVID-19 vaccine, and PaxlovidTM (nirmatrelvir tablets/ritonavir tablets), a COVID-19 therapeutic, are benchmarks for accelerated innovation during a global pandemic. Rapid choice of the SARS-CoV-2 spike protein and main protease (Mpro) as targets for the vaccine and therapeutic, respectively, leveraged the available knowledge of the biology of SARS-CoV-2 and related viruses. The nonclinical immunogenicity and safety of BNT162b2 was rigorously assessed. Likewise, a comprehensive nonclinical safety assessment...
Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Nasir Khan Jean Sathish Cynthia M Rohde Source Type: research
