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pmid:27095044

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

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 I Özcebe · Yahya Büyükaşık · Hakan Göker

Turkish journal of haematology : official journal of Turkish Society of Haematology · 2016 doi:10.4274/tjh.2015.0145

Paper

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Experiment

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Data

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Analysis

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title
Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma.
doi
10.4274/tjh.2015.0145
pmid
27095044
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[0]
Mehdi Ghasemi
[1]
Semih Alpsoy
[2]
Seyhan Türk
[3]
Ümit Y Malkan
[4]
Şükrü Atakan
[5]
İbrahim C Haznedaroğlu
[6]
Gürsel Güneş
[7]
Mehmet Gündüz
[8]
Burak Yılmaz
[9]
Sezgin Etgül
[10]
Seda Aydın
[11]
Tuncay Aslan
[12]
Nilgün Sayınalp
[13]
Salih Aksu
[14]
Haluk Demiroğlu
[15]
Osman I Özcebe
[16]
Yahya Büyükaşık
[17]
Hakan Göker
journal
Turkish journal of haematology : official journal of Turkish Society of Haematology
year
2016
abstract
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 regression-based 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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Our linear regression model identified 73 genes.
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Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project.
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Complete file
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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.\nMATERIALS 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 regression-based 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.\nRESULTS: 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.\nCONCLUSION: 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.", "claims": [{"id": "claim-method", "statement": "To do that, a linear regression model was used to discover genes whose expression profiles correlated with bortezomib sensitivity as measured for 7 myeloma cell lines by IC50 values from the Genomics of Drug Sensitivity in Cancer database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27095044", "locator": "sections[5] \"In Silico Classification of Myeloma Cell Lines and Identification of Candidate Gene Biomarkers\" paragraph 2", "quote": "To do that, a linear regression model was used to discover genes whose expression profiles correlated with bortezomib sensitivity as measured for 7 myeloma cell lines by IC50 values from the Genomics of Drug Sensitivity in Cancer database."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The myeloma cell line expression data were retrieved from ArrayExpress (E-MTAB-783) and consisted of transcriptomic profiles of 789 cancer cell lines from various types of cancer.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27095044", "locator": "sections[3] \"Public Expression and Drug Cytotoxicity Data\" paragraph 2", "quote": "The myeloma cell line expression data were retrieved from ArrayExpress (E-MTAB-783) and consisted of transcriptomic profiles of 789 cancer cell lines from various types of cancer."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our linear regression model identified 73 genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:27095044", "locator": "sections[6] \"RESULTS\" paragraph 2", "quote": "Our linear regression model identified 73 genes."}, {"asset": "source:pmid:27095044", "locator": "sections[5] \"In Silico Classification of Myeloma Cell Lines and Identification of Candidate Gene Biomarkers\" paragraph 2", "quote": "To do that, a linear regression model was used to discover genes whose expression profiles correlated with bortezomib sensitivity as measured for 7 myeloma cell lines by IC50 values from the Genomics of Drug Sensitivity in Cancer database."}, {"asset": "source:pmid:27095044", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "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."}, {"asset": "source:pmid:27095044", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our linear regression model identified 73 genes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:27095044"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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