Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients
Understanding the molecular mechanisms underlying the pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is a major challenge. We used co-expression networks implemented by the SWitch Miner software to identify switch genes associated with drastic transcrip...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/7150 |
| _version_ | 1797527979629215744 |
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| author | Jose A. Santiago James P. Quinn Judith A. Potashkin |
| author_facet | Jose A. Santiago James P. Quinn Judith A. Potashkin |
| author_sort | Jose A. Santiago |
| collection | DOAJ |
| description | Understanding the molecular mechanisms underlying the pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is a major challenge. We used co-expression networks implemented by the SWitch Miner software to identify switch genes associated with drastic transcriptomic changes in the blood of ALS patients. Functional analyses revealed that switch genes were enriched in pathways related to the cell cycle, hepatitis C, and small cell lung cancer. Analysis of switch genes by sex revealed that switch genes from males were associated with metabolic pathways, including PI3K-AKT, sphingolipid, carbon metabolism, FOXO, and AMPK signaling. In contrast, female switch genes related to infectious diseases, inflammation, apoptosis, and atherosclerosis. Furthermore, eight switch genes showed sex-specific gene expression patterns. Collectively, we identified essential genes and pathways that may explain sex differences observed in ALS. Future studies investigating the potential role of these genes in driving disease disparities between males and females with ALS are warranted. |
| first_indexed | 2024-03-10T09:51:34Z |
| format | Article |
| id | doaj.art-2bea4f1c386640dab797db63e88f6d59 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:51:34Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2bea4f1c386640dab797db63e88f6d592023-11-22T02:41:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012213715010.3390/ijms22137150Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis PatientsJose A. Santiago0James P. Quinn1Judith A. Potashkin2NeuroHub Analytics, LLC, Chicago, IL 60605, USAQ Regulating Systems, LLC, Gurnee, IL 60031, USACenter for Neurodegenerative Diseases and Therapeutics, Cellular and Molecular Pharmacology Department, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USAUnderstanding the molecular mechanisms underlying the pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is a major challenge. We used co-expression networks implemented by the SWitch Miner software to identify switch genes associated with drastic transcriptomic changes in the blood of ALS patients. Functional analyses revealed that switch genes were enriched in pathways related to the cell cycle, hepatitis C, and small cell lung cancer. Analysis of switch genes by sex revealed that switch genes from males were associated with metabolic pathways, including PI3K-AKT, sphingolipid, carbon metabolism, FOXO, and AMPK signaling. In contrast, female switch genes related to infectious diseases, inflammation, apoptosis, and atherosclerosis. Furthermore, eight switch genes showed sex-specific gene expression patterns. Collectively, we identified essential genes and pathways that may explain sex differences observed in ALS. Future studies investigating the potential role of these genes in driving disease disparities between males and females with ALS are warranted.https://www.mdpi.com/1422-0067/22/13/7150ALSbloodco-expression networksneurodegenerationswitch genessex differences |
| spellingShingle | Jose A. Santiago James P. Quinn Judith A. Potashkin Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients International Journal of Molecular Sciences ALS blood co-expression networks neurodegeneration switch genes sex differences |
| title | Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients |
| title_full | Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients |
| title_fullStr | Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients |
| title_full_unstemmed | Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients |
| title_short | Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients |
| title_sort | network analysis identifies sex specific gene expression changes in blood of amyotrophic lateral sclerosis patients |
| topic | ALS blood co-expression networks neurodegeneration switch genes sex differences |
| url | https://www.mdpi.com/1422-0067/22/13/7150 |
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