Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma

Objective: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was...

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Main Authors: Mehdi Ghasemi, Semih Alpsoy, Seyhan Türk, Ümit Y. Malkan, Şükrü Atakan, İbrahim C. Haznedaroğlu, Gürsel Güneş, Mehmet Gündüz, Burak Yılmaz, Sezgin Etgül, Seda Aydın, Tuncay Aslan, Nilgün Sayınalp, Salih Aksu, Haluk Demiroğlu, Osman İ. Özcebe, Yahya Büyükaşık, Hakan Göker
Format: Article
Language:English
Published: Galenos Publishing House 2016-11-01
Series:Turkish Journal of Hematology
Subjects:
Online Access:https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-98105
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author Mehdi Ghasemi
Semih Alpsoy
Seyhan Türk
Ümit Y. Malkan
Şükrü Atakan
İbrahim C. Haznedaroğlu
Gürsel Güneş
Mehmet Gündüz
Burak Yılmaz
Sezgin Etgül
Seda Aydın
Tuncay Aslan
Nilgün Sayınalp
Salih Aksu
Haluk Demiroğlu
Osman İ. Özcebe
Yahya Büyükaşık
Hakan Göker
author_facet Mehdi Ghasemi
Semih Alpsoy
Seyhan Türk
Ümit Y. Malkan
Şükrü Atakan
İbrahim C. Haznedaroğlu
Gürsel Güneş
Mehmet Gündüz
Burak Yılmaz
Sezgin Etgül
Seda Aydın
Tuncay Aslan
Nilgün Sayınalp
Salih Aksu
Haluk Demiroğlu
Osman İ. Özcebe
Yahya Büyükaşık
Hakan Göker
author_sort Mehdi Ghasemi
collection DOAJ
description Objective: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib. Materials and Methods: We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was 'Robust Multi-array analysis' normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regressionbased approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis. Results: Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. Conclusion: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.
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spelling doaj.art-f4f9f90b278148459d1e22d2fc9074ff2023-02-15T16:09:16ZengGalenos Publishing HouseTurkish Journal of Hematology1308-52632016-11-0133428629210.4274/tjh.2015.0145TJH-98105Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple MyelomaMehdi Ghasemi0Semih Alpsoy1Seyhan Türk2Ümit Y. Malkan3Şükrü Atakan4İbrahim C. Haznedaroğlu5Gürsel Güneş6Mehmet Gündüz7Burak Yılmaz8Sezgin Etgül9Seda Aydın10Tuncay Aslan11Nilgün Sayınalp12Salih Aksu13Haluk Demiroğlu14Osman İ. Özcebe15Yahya Büyükaşık16Hakan Göker17Sentegen Biotechnology, Ankara, Turkey, Bilkent University Faculty of Science, Department of Molecular Biology and Genetics, Ankara, TurkeySentegen Biotechnology, Ankara, Turkey, METU Graduate School of Informatics Institute, Health Informatics Program, Clinic of Bioinformatics, Ankara, TurkeyHacettepe University Faculty of Pharmacy, Department of Biochemistry, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeySentegen Biotechnology, Ankara, Turkey, Bilkent University Faculty of Science, Department of Molecular Biology and Genetics, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyAtatürk Training and Research Hospital, Clinic of Hematology, Ankara, TurkeySentegen Biotechnology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, TurkeyObjective: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib. Materials and Methods: We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was 'Robust Multi-array analysis' normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regressionbased approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis. Results: Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. Conclusion: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-98105expression profiles of the individual genes corresponding to the genes generated by cytotoxicity experiments with bortezomib in multiple myeloma
spellingShingle Mehdi Ghasemi
Semih Alpsoy
Seyhan Türk
Ümit Y. Malkan
Şükrü Atakan
İbrahim C. Haznedaroğlu
Gürsel Güneş
Mehmet Gündüz
Burak Yılmaz
Sezgin Etgül
Seda Aydın
Tuncay Aslan
Nilgün Sayınalp
Salih Aksu
Haluk Demiroğlu
Osman İ. Özcebe
Yahya Büyükaşık
Hakan Göker
Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma
Turkish Journal of Hematology
expression profiles of the individual genes corresponding to the genes generated by cytotoxicity experiments with bortezomib in multiple myeloma
title Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma
title_full Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma
title_fullStr Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma
title_full_unstemmed Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma
title_short Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma
title_sort expression profiles of the individual genes corresponding to the genes generated by cytotoxicity experiments with bortezomib in multiple myeloma
topic expression profiles of the individual genes corresponding to the genes generated by cytotoxicity experiments with bortezomib in multiple myeloma
url https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-98105
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