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Article ; Online: Phosprof: pathway analysis database of drug response based on phosphorylation activity measurements.

Kagiwada, Harumi / Motono, Chie / Horimoto, Katsuhisa / Fukui, Kazuhiko

Database : the journal of biological databases and curation

2022 Volume 2022

Abstract: Protein phosphorylation plays a fundamental role in many cellular processes. Proteins are phosphorylated by kinases, which have been studied as drug targets for the treatment of various diseases, particularly cancer. Because kinases have multiple roles ... ...

Abstract	Protein phosphorylation plays a fundamental role in many cellular processes. Proteins are phosphorylated by kinases, which have been studied as drug targets for the treatment of various diseases, particularly cancer. Because kinases have multiple roles in interconnected molecular pathways, their specific regulation is required to enhance beneficial and reduce adversarial effects of drugs. Using our previously developed platform, we measured phosphorylation profiles of MCF7 and K562 cells treated with 94 clinical drugs. These phosphorylation profiles can provide insights into pathway activities and biological functions. Here, we introduce Phosprof, a novel database of drug response based on phosphorylation activity. Phosprof is able to present up- or downregulated phosphorylated signature proteins on pathway maps, significant pathways on the hierarchal tree in signal transduction and commonly perturbed pathways affected by the selected drugs. It also serves as a useful web interface for new or known drug profile search based on their molecular similarity with the 94 drugs. Phosprof can be helpful for further investigation of drug responses in terms of phosphorylation by utilizing the various approved drugs whose target phenotypes are known. Database url: https://phosprof.medals.jp/.
MeSH term(s)	Databases, Factual ; Phosphorylation ; Proteins ; Signal Transduction/genetics
Chemical Substances	Proteins
Language	English
Publishing date	2022-08-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2496706-3
ISSN	1758-0463 ; 1758-0463
ISSN (online)	1758-0463
ISSN	1758-0463
DOI	10.1093/database/baac072
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Application of multiple omics and network projection analyses to drug repositioning for pathogenic mosquito-borne viruses.

Amemiya, Takayuki / Horimoto, Katsuhisa / Fukui, Kazuhiko

Scientific reports

2021 Volume 11, Issue 1, Page(s) 10136

Abstract: Pathogenic mosquito-borne viruses are a serious public health issue in tropical and subtropical regions and are increasingly becoming a problem in other climate zones. Drug repositioning is a rapid, pharmaco-economic approach that can be used to identify ...

Abstract	Pathogenic mosquito-borne viruses are a serious public health issue in tropical and subtropical regions and are increasingly becoming a problem in other climate zones. Drug repositioning is a rapid, pharmaco-economic approach that can be used to identify compounds that target these neglected tropical diseases. We have applied a computational drug repositioning method to five mosquito-borne viral infections: dengue virus (DENV), zika virus (ZIKV), West Nile virus (WNV), Japanese encephalitis virus (JEV) and Chikungunya virus (CHIV). We identified signature molecules and pathways for each virus infection based on omics analyses, and determined 77 drug candidates and 146 proteins for those diseases by using a filtering method. Based on the omics analyses, we analyzed the relationship among drugs, target proteins and the five viruses by projecting the signature molecules onto a human protein-protein interaction network. We have classified the drug candidates according to the degree of target proteins in the protein-protein interaction network for the five infectious diseases.
MeSH term(s)	Animals ; Computational Biology/methods ; Drug Repositioning ; Gene Regulatory Networks/drug effects ; Genomics/methods ; Host-Pathogen Interactions/genetics ; Humans ; Metabolomics/methods ; Proteomics/methods ; Signal Transduction/drug effects ; Vector Borne Diseases/drug therapy ; Vector Borne Diseases/etiology ; Vector Borne Diseases/metabolism
Language	English
Publishing date	2021-05-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-89171-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Relationship between regulatory pattern of gene expression level and gene function.

Inoue, Masayo / Horimoto, Katsuhisa

PloS one

2017 Volume 12, Issue 5, Page(s) e0177430

Abstract: Regulation of gene expression levels is essential for all living systems and transcription factors (TFs) are the main regulators of gene expression through their ability to repress or induce transcription. A balance between synthesis and degradation ... ...

Abstract	Regulation of gene expression levels is essential for all living systems and transcription factors (TFs) are the main regulators of gene expression through their ability to repress or induce transcription. A balance between synthesis and degradation rates controls gene expression levels. To determine which rate is dominant, we analyzed the correlation between expression levels of a TF and its regulated gene based on a mathematical model. We selected about 280,000 expression patterns of 355 TFs and 647 regulated genes using DNA microarray data from the Gene Expression Omnibus (GEO) data repository. Based on our model, correlation between the expressions of TF-regulated gene pairs corresponds to tuning of the synthesis rate, whereas no correlation indicates excessive synthesis and requires tuning of the degradation rate. The gene expression relationships between TF-regulated gene pairs were classified into four types that correspond to different gene regulatory mechanisms. It was surprising that fewer than 20% of these genes were governed by the familiar regulatory mechanism, i.e., through the synthesis rate. Moreover, we performed pathway analysis and found that each classification type corresponded to distinct gene functions: cellular regulation pathways were dominant in the type with synthesis rate regulation and terms associated with diseases such as cancer, Parkinson's disease, and Alzheimer's disease were dominant in the type with degradation rate regulation. Interestingly, these diseases are caused by the accumulation of proteins. These results indicated that gene expression is regulated structurally, not arbitrarily, according to the gene function. This funding is indicative of a systematic control of transcription processes at the whole-cell level.
MeSH term(s)	Algorithms ; Gene Expression Profiling ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Humans ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Transcription Factors/genetics
Chemical Substances	Transcription Factors
Language	English
Publishing date	2017-05-11
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0177430
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Lansoprazole inhibits the development of sessile serrated lesions by inducing G1 arrest via Skp2/p27 signaling pathway.

Kawaguchi, Tomoyuki / Okamoto, Koichi / Fujimoto, Shota / Bando, Masahiro / Wada, Hironori / Miyamoto, Hiroshi / Sato, Yasushi / Muguruma, Naoki / Horimoto, Katsuhisa / Takayama, Tetsuji

Journal of gastroenterology

2023 Volume 59, Issue 1, Page(s) 11–23

Abstract: Background: Although the serrated-neoplasia pathway reportedly accounts for 15-30% of colorectal cancer (CRC), no studies on chemoprevention of sessile serrated lesions (SSLs) have been reported. We searched for effective compounds comprehensively from ... ...

Abstract	Background: Although the serrated-neoplasia pathway reportedly accounts for 15-30% of colorectal cancer (CRC), no studies on chemoprevention of sessile serrated lesions (SSLs) have been reported. We searched for effective compounds comprehensively from a large series of compounds by employing Connectivity Map (CMAP) analysis of SSL-specific gene expression profiles coupled with in vitro screening using SSL patient-derived organoids (PDOs), and validated their efficacy using a xenograft mouse model of SSL. Methods: We generated SSL-specific gene signatures based on DNA microarray data, and applied them to CMAP analysis with 1309 FDA-approved compounds to select candidate compounds. We evaluated their inhibitory effects on SSL-PDOs using a cell viability assay. SSL-PDOs were orthotopically transplanted into NOG mice for in vivo evaluation. The signal transduction pathway was evaluated by gene expression profile and protein expression analysis. Results: We identified 221 compounds by employing CMAP analysis of SSL-specific signatures, which should cancel the gene signatures, and narrowed them down to 17 compounds. Cell viability assay using SSL-PDOs identified lansoprazole as having the lowest IC50 value (47 µM) among 17 compounds. When SSL-PDO was orthotopically transplanted into murine intestinal tract, the tumor grew gradually. Administration of lansoprazole to mice inhibited the growth of SSL xenograft whereas the tumor in control mice treated with vehicle alone grew gradually over time. The Ki67 index in xenograft lesions from the lansoprazole group was significantly lower compared with the control group. Cell cycle analysis of SSL-PDOs treated with lansoprazole exhibited a significant increase in G1 phase cell population. Microarray and protein analysis revealed that lansoprazole downregulated Skp2 expression and upregulated p27 expression in SSL-PDOs. Conclusions: Our data strongly suggest that lansoprazole is the most effective chemopreventive agent against SSL, and that lansoprazole induces G1 cell cycle arrest by downregulating Skp2 and upregulating p27 in SSL cells.
MeSH term(s)	Humans ; Animals ; Mice ; G1 Phase ; Signal Transduction ; Neoplasms ; Colorectal Neoplasms/genetics
Language	English
Publishing date	2023-11-22
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1186495-3
ISSN	1435-5922 ; 0944-1174
ISSN (online)	1435-5922
ISSN	0944-1174
DOI	10.1007/s00535-023-02052-0
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Book ; Conference proceedings: Algebraic Biology

Horimoto, Katsuhisa

third international conference, AB 2008, Castle of Hagenberg, Austria, July 31-August 2, 2008 : proceedings

(Lecture notes in computer science, ; 5147 ; LNCS sublibrary. SL 1, Theoretical computer science and general issues)

2008

Title variant	AB 2008
Event/congress	AB 2008 (2008, HagenbergimMühlkreisAustria)
Author's details	Katsuhisa Horimoto ... [et al.], eds
Series title	Lecture notes in computer science, ; 5147 ; LNCS sublibrary. SL 1, Theoretical computer science and general issues
Keywords	Biomathematics ; Computational biology ; Bioinformatics
Language	English
Size	xii, 244 p. :, ill. ;, 24 cm.
Publisher	Springer
Publishing place	Berlin ; New York
Document type	Book ; Conference proceedings
ISBN	9783540851004 ; 3540851003
Database	NAL-Catalogue (AGRICOLA)

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Book ; Conference proceedings ; Online: Algebraic biology

Horimoto, Katsuhisa

third international conference, AB 2008, Castle of Hagenberg, Austria, July 31 - August 2, 2008 ; proceedings

(Lecture notes in computer science ; 5147)

2008

Institution	AB
Event/congress	AB (3, 2008.07.31-08.02, CastleofHagenberg) ; International Conference on Algebraic Biology (3, 2008.07.31-08.02, CastleofHagenberg)
Author's details	Katsuhisa Horimoto ... (eds.)
Series title	Lecture notes in computer science ; 5147
Keywords	Bioinformatics ; Biomathematics ; Computational biology
Language	English
Size	Online-Ressource (XII, 244 S.)
Publisher	Springer
Publishing place	Berlin u.a.
Document type	Book ; Conference proceedings ; Online
Note	Literaturangaben
ISBN	3540851003 ; 9783540851004 ; 9783540851011 ; 3540851011
DOI	10.1007/978-3-540-85101-1
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Book ; Conference proceedings ; Online: Algebraic biology

Horimoto, Katsuhisa

third international conference, AB 2008, Castle of Hagenberg, Austria, July 31 - August 2, 2008 ; proceedings

(Lecture notes in computer science ; 5147)

2008

Institution	AB
Event/congress	AB (3, 2008.07.31-08.02, CastleofHagenberg) ; International Conference on Algebraic Biology (3, 2008.07.31-08.02, CastleofHagenberg)
Author's details	Katsuhisa Horimoto ... (eds.)
Series title	Lecture notes in computer science ; 5147
Keywords	Bioinformatics ; Biomathematics ; Computational biology
Language	English
Size	Online-Ressource (XII, 244 S.)
Publisher	Springer
Publishing place	Berlin u.a.
Document type	Book ; Conference proceedings ; Online
Note	Literaturangaben
ISBN	3540851003 ; 9783540851004 ; 9783540851011 ; 3540851011
DOI	10.1007/978-3-540-85101-1
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Assessing the activation/inhibition of tyrosine kinase-related pathways with a newly developed platform.

Kagiwada, Harumi / Kiboku, Takayuki / Matsuo, Hitomi / Kitazawa, Masashi / Fukui, Kazuhiko / Horimoto, Katsuhisa

Proteomics

2021 Volume 21, Issue 16, Page(s) e2000251

Abstract: The phosphorylation of cellular proteins plays a crucial role in the transduction of various signals from outside the cell into the nucleus. The signals are transduced by phosphorylation chain reactions within multiple pathways; however, determining ... ...

Abstract	The phosphorylation of cellular proteins plays a crucial role in the transduction of various signals from outside the cell into the nucleus. The signals are transduced by phosphorylation chain reactions within multiple pathways; however, determining which pathways are responsible for each defined signal has proven challenging. To estimate the activity of each pathway, we developed a phosphorylation array platform comprising a protein array with 1200 proteins belonging to 376 signalling pathways and an analytical method to estimate pathway activity based on the phosphorylation levels of proteins. The performance of our system was assessed by reconstructing kinase-substrate relationships, as well as by estimating pathway activity upon epidermal growth factor (EGF) stimulation and the pharmacological inhibition of epidermal growth factor receptor (EGFR). As a result, kinase-substrate relationships were reliably reconstructed based on the precise measurement of phosphorylation levels of constituent proteins on the array. Furthermore, the pathway activities associated with EGF stimulation and EGFR inhibition were successfully traced through the related pathways from the outer membrane to the nucleus along a time course. Thus, our phosphorylation array system can effectively assess the activity of specific signalling pathways that are perturbed by extracellular stimuli, such as various drugs.
MeSH term(s)	Epidermal Growth Factor/metabolism ; Phosphorylation ; Protein Binding ; Protein-Tyrosine Kinases/metabolism ; Signal Transduction ; Tyrosine/metabolism
Chemical Substances	Tyrosine (42HK56048U) ; Epidermal Growth Factor (62229-50-9) ; Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2021-06-27
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2032093-0
ISSN	1615-9861 ; 1615-9853
ISSN (online)	1615-9861
ISSN	1615-9853
DOI	10.1002/pmic.202000251
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 5386: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Drug repositioning for dengue haemorrhagic fever by integrating multiple omics analyses.

Amemiya, Takayuki / Gromiha, M Michael / Horimoto, Katsuhisa / Fukui, Kazuhiko

Scientific reports

2019 Volume 9, Issue 1, Page(s) 523

Abstract: To detect drug candidates for dengue haemorrhagic fever (DHF), we employed a computational drug repositioning method to perform an integrated multiple omics analysis based on transcriptomic, proteomic, and interactomic data. We identified 3,892 ... ...

Abstract	To detect drug candidates for dengue haemorrhagic fever (DHF), we employed a computational drug repositioning method to perform an integrated multiple omics analysis based on transcriptomic, proteomic, and interactomic data. We identified 3,892 significant genes, 389 proteins, and 221 human proteins by transcriptomic analysis, proteomic analysis, and human-dengue virus protein-protein interactions, respectively. The drug candidates were selected using gene expression profiles for inverse drug-disease relationships compared with DHF patients and healthy controls as well as interactomic relationships between the signature proteins and chemical compounds. Integrating the results of the multiple omics analysis, we identified eight candidates for drug repositioning to treat DHF that targeted five proteins (ACTG1, CALR, ERC1, HSPA5, SYNE2) involved in human-dengue virus protein-protein interactions, and the signature proteins in the proteomic analysis mapped to significant pathways. Interestingly, five of these drug candidates, valparoic acid, sirolimus, resveratrol, vorinostat, and Y-27632, have been reported previously as effective treatments for flavivirus-induced diseases. The computational approach using multiple omics data for drug repositioning described in this study can be used effectively to identify novel drug candidates.
MeSH term(s)	Computational Biology/methods ; Drug Repositioning/methods ; Humans ; Molecular Targeted Therapy/methods ; Protein Interaction Maps/drug effects ; Severe Dengue/drug therapy ; Severe Dengue/genetics ; Severe Dengue/metabolism ; Transcriptome/drug effects
Language	English
Publishing date	2019-01-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-36636-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: ToGo-WF: prediction of RNA tertiary structures and RNA-RNA/protein interactions using the KNIME workflow.

Yamasaki, Satoshi / Amemiya, Takayuki / Yabuki, Yukimitsu / Horimoto, Katsuhisa / Fukui, Kazuhiko

Journal of computer-aided molecular design

2019 Volume 33, Issue 5, Page(s) 497–507

Abstract: Recent progress in molecular biology has revealed that many non-coding RNAs regulate gene expression or catalyze biochemical reactions in tumors, viruses and several other diseases. The tertiary structure of RNA molecules and RNA-RNA/protein interaction ... ...

Abstract	Recent progress in molecular biology has revealed that many non-coding RNAs regulate gene expression or catalyze biochemical reactions in tumors, viruses and several other diseases. The tertiary structure of RNA molecules and RNA-RNA/protein interaction sites are of increasing importance as potential targets for new medicines that treat a broad array of human diseases. Current RNA drugs are split into two groups: antisense RNA molecules and aptamers. In this report, we present a novel workflow to predict RNA tertiary structures and RNA-RNA/protein interactions using the KNIME environment, which enabled us to assemble a combination of RNA-related analytical tools and databases. In this study, three analytical workflows for comprehensive structural analysis of RNA are introduced: (1) prediction of the tertiary structure of RNA; (2) prediction of the structure of RNA-RNA complexes and analysis of their interactions; and (3) prediction of the structure of RNA-protein complexes and analysis of their interactions. In an RNA-protein case study, we modeled the tertiary structure of pegaptanib, an aptamer drug, and performed docking calculations of the pegaptanib-vascular endothelial growth factor complex using a fragment of the interaction site of the aptamer. We also present molecular dynamics simulations of the RNA-protein complex to evaluate the affinity of the complex by mutating bases at the interaction interface. The results provide valuable information for designing novel features of aptamer-protein complexes.
MeSH term(s)	Aptamers, Nucleotide/chemistry ; Aptamers, Nucleotide/pharmacology ; Base Sequence ; Humans ; Models, Molecular ; Nucleic Acid Conformation ; Protein Binding ; RNA/chemistry ; RNA/metabolism ; Software ; Vascular Endothelial Growth Factor A/metabolism ; Workflow
Chemical Substances	Aptamers, Nucleotide ; Vascular Endothelial Growth Factor A ; pegaptanib (2H1PA8H1EN) ; RNA (63231-63-0)
Keywords	covid19
Language	English
Publishing date	2019-03-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	808166-9
ISSN	1573-4951 ; 0920-654X
ISSN (online)	1573-4951
ISSN	0920-654X
DOI	10.1007/s10822-019-00195-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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