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multiomics_analysis_for_dementia [2020/06/26 19:26] – [Related work] adminmultiomics_analysis_for_dementia [2021/04/08 17:56] – [Subprojects] isha
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 Determine biomarkers for Alzheimer's and other neurodegenerative diseases using comprehensive analysis of multi-omics data including genomics, epigenomics, metabolomics, proteomics, etc. Determine biomarkers for Alzheimer's and other neurodegenerative diseases using comprehensive analysis of multi-omics data including genomics, epigenomics, metabolomics, proteomics, etc.
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   - The Brain eQTL Almanac ([[http://braineac.org/|Braineac]]) generated by UK Brain Expression Consortium (UKBEC) "comprises of genomic and transcriptome data of 134 brains from individuals free of neurodegenerative disorders. Up to 12 brain regions were extracted per brain in parallel for mRNA quantification."   - The Brain eQTL Almanac ([[http://braineac.org/|Braineac]]) generated by UK Brain Expression Consortium (UKBEC) "comprises of genomic and transcriptome data of 134 brains from individuals free of neurodegenerative disorders. Up to 12 brain regions were extracted per brain in parallel for mRNA quantification."
   - Omics data were generated in [[https://www.neurodegenerationresearch.eu/it/cohort/the-rhineland-study/|Rhineland]] Study including DNA methylation from ~2K blood samples. Aslam Imtiaz presented these data in the NeuroCHARGE call on 2019-11-07.   - Omics data were generated in [[https://www.neurodegenerationresearch.eu/it/cohort/the-rhineland-study/|Rhineland]] Study including DNA methylation from ~2K blood samples. Aslam Imtiaz presented these data in the NeuroCHARGE call on 2019-11-07.
 +  - [[https://bmbls.bmi.osumc.edu/scread/|scREAD]]: A Single-Cell RNA-Seq Database for Alzheimer’s Disease ([[https://www.cell.com/iscience/pdf/S2589-0042(20)30966-4.pdf|pdf]]). It covers 73 datasets from 15 studies, 10 brain regions, 713640 cells.Useful for: a) listing available datasets, b) easy preliminary DE analysis across cell types and disease vs. control conditions.
  
  
 ===== Collaborators ===== ===== Collaborators =====
  
-Dr. [[http://gsbs.uthscsa.edu/faculty/sudha-seshadri-m.d.-dm|Sudha Seshadri]], the Founding Director of The Glenn [[https://biggsinstitute.org/|Biggs Institute]] for Alzheimer's & Neurodegenerative Diseases, [[https://biggsinstitute.org/team-member/claudia-l-satizabal-phd/|Dr. Claudia Satizabal]], Dr. [[http://runewarkbiology.rutgers.edu/Dobrowolski Lab/index.html|Radek Dobrowolski]], and Dr. [[https://biggsinstitute.org/team-member/qitao-ran/|Qitao Ran]].+Dr. [[http://gsbs.uthscsa.edu/faculty/sudha-seshadri-m.d.-dm|Sudha Seshadri]], the Founding Director of The Glenn [[https://biggsinstitute.org/|Biggs Institute]] for Alzheimer's & Neurodegenerative Diseases, [[https://biggsinstitute.org/team-member/claudia-l-satizabal-phd/|Dr. Claudia Satizabal]], Dr. [[http://runewarkbiology.rutgers.edu/Dobrowolski Lab/index.html|Radek Dobrowolski]], Dr. [[https://biggsinstitute.org/team-member/qitao-ran/|Qitao Ran]], and Dr. [[https://school.wakehealth.edu/Faculty/O/Miranda-E-Orr|Miranda Orr]] from Wake Forest University.
  
  
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   - Network analysis on [[https://docs.google.com/document/d/1K89u6OubQUXAycg6JaEqzNgv18ybRy4QWcG_3UVQBuQ/edit|proteome]] data of Fremingham cohort.   - Network analysis on [[https://docs.google.com/document/d/1K89u6OubQUXAycg6JaEqzNgv18ybRy4QWcG_3UVQBuQ/edit|proteome]] data of Fremingham cohort.
   - [[https://docs.google.com/presentation/d/1gCs39bst5xqxbpLNybRkJg1hUxxWCspmhlvKfdjtTsw/edit?ts=5d41b329#slide=id.g5e1f444b4f_0_0|DE]] analysis on RNA-Seq data of 5xFAD and Gpx4Tg mouse models for AD. Four biological replicates in each of the four conditions were generated in Ran's Lab.   - [[https://docs.google.com/presentation/d/1gCs39bst5xqxbpLNybRkJg1hUxxWCspmhlvKfdjtTsw/edit?ts=5d41b329#slide=id.g5e1f444b4f_0_0|DE]] analysis on RNA-Seq data of 5xFAD and Gpx4Tg mouse models for AD. Four biological replicates in each of the four conditions were generated in Ran's Lab.
 +  - Identify senescent cells and their characteristics in human brain.
 +  - Assess the effect of lowering expression of CD33 in microglia on AD phenotypes through [[https://docs.google.com/document/d/1-SStE--v9-ATh1Bi9zqEXaTDD21kX2KjyQ1J6c0Ww74/edit|analysis]] of single cell RNA-Seq data.
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 +===== Related work =====
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 +  - An interactive **timeline**  of Alzheimer's disease by [[https://www.alzforum.org/timeline/alzheimers-disease#2010|AlzForum]].
 +  - Satizabal, Claudia L., et al. "Genetic architecture of subcortical brain structures in 38,851 individuals." //[[https://www.nature.com/articles/s41588-019-0511-y|Nature genetics]]// 51.11 (2019): 1624-1636. \\ They identified a set of genes that is "significantly enriched for //Drosophila//  orthologs associated with neurodevelopmental phenotypes".
 +  - Yamazaki, Yu., et al. "Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies." [[https://www.nature.com/articles/s41582-019-0228-7|Nat Rev Neurol ]](2019): 501–518.
 +  - Ferreira, Daniel., et al. Biological subtypes of Alzheimer disease: A systematic review and meta-analysis [[https://n.neurology.org/content/neurology/early/2020/02/11/WNL.0000000000009058.full.pdf|Neurology]] (2020):94:1-13.
 +  - Sey, Nancy YA, et al. A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles. [[https://www.nature.com/articles/s41593-020-0603-0|Nature Neuroscience]], 2020.
 +  - Borghesan, M., et al. "A **Senescence**-Centric View of Aging: Implications for Longevity and Disease." [[https://www.sciencedirect.com/science/article/abs/pii/S0962892420301434|Trends in Cell Biology]] (2020). The review paper suggested by Christi.
  
  
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   - An interactive **timeline**  of Alzheimer's disease by [[https://www.alzforum.org/timeline/alzheimers-disease#2010|AlzForum]].   - An interactive **timeline**  of Alzheimer's disease by [[https://www.alzforum.org/timeline/alzheimers-disease#2010|AlzForum]].
-  - Satizabal, Claudia L., et al. "Genetic architecture of subcortical brain structures in 38,851 individuals." //[[https://www.nature.com/articles/s41588-019-0511-y|Nature genetics]] //51.11 (2019): 1624-1636. \\ They identified a set of genes that is "significantly enriched for //Drosophila//  orthologs associated with neurodevelopmental phenotypes".+  - Satizabal, Claudia L., et al. "Genetic architecture of subcortical brain structures in 38,851 individuals." //[[https://www.nature.com/articles/s41588-019-0511-y|Nature genetics]]// 51.11 (2019): 1624-1636. \\ They identified a set of genes that is "significantly enriched for //Drosophila//  orthologs associated with neurodevelopmental phenotypes".
   - Yamazaki, Yu., et al. "Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies." [[https://www.nature.com/articles/s41582-019-0228-7|Nat Rev Neurol ]](2019): 501–518.   - Yamazaki, Yu., et al. "Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies." [[https://www.nature.com/articles/s41582-019-0228-7|Nat Rev Neurol ]](2019): 501–518.
   - Ferreira, Daniel., et al. Biological subtypes of Alzheimer disease: A systematic review and meta-analysis [[https://n.neurology.org/content/neurology/early/2020/02/11/WNL.0000000000009058.full.pdf|Neurology]] (2020):94:1-13.   - Ferreira, Daniel., et al. Biological subtypes of Alzheimer disease: A systematic review and meta-analysis [[https://n.neurology.org/content/neurology/early/2020/02/11/WNL.0000000000009058.full.pdf|Neurology]] (2020):94:1-13.
   - Sey, Nancy YA, et al. A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles. [[https://www.nature.com/articles/s41593-020-0603-0|Nature Neuroscience]], 2020.   - Sey, Nancy YA, et al. A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles. [[https://www.nature.com/articles/s41593-020-0603-0|Nature Neuroscience]], 2020.
 +  - Borghesan, M., et al. "A **Senescence**-Centric View of Aging: Implications for Longevity and Disease." [[https://www.sciencedirect.com/science/article/abs/pii/S0962892420301434|Trends in Cell Biology]] (2020). The review paper suggested by Christi.