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multiomics_analysis_for_dementia [2020/06/26 22:26]
admin [Related work]
multiomics_analysis_for_dementia [2021/04/23 21:55] (current)
admin [Data]
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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 Cohorts for Heart and Aging Research in Genomic Epidemiology ([[http://​www.chargeconsortium.com|CHARGE]]) Consortium.   - The Cohorts for Heart and Aging Research in Genomic Epidemiology ([[http://​www.chargeconsortium.com|CHARGE]]) Consortium.
-  - The Trans-Omics for Precision Medicine ([[https://​www.nhlbiwgs.org|TOPMed]]) program. The TOPMed Omics [[http://​oncinfo.org/​_media/​wiki:​topmed_omics_survey.pdf|Survey]] in 2017 includes Framingham Heart Study (FHS) details, which are described clearer in [[http://​oncinfo.org/​_media/​wiki:​omics_fhs.pdf|2016]]. [[https://​www.ncbi.nlm.nih.gov/​projects/​gap/​cgi-bin/​molecular.cgi?​study_id=phs000363.v17.p11&​phv=173423&​phd=4119&​pha=&​pht=2941&​phvf=&​phdf=&​phaf=&​phtf=&​dssp=1&​consent=&​temp=1|SABRe]] is a substudy of FHS and has mRNA and miRNA data. We obtained [[https://​docs.google.com/​document/​d/​1B8uKY2QBuJHAiPrv9y_cR9704RrI7nZM71oVc7jt5Q8/​edit|these]] data in 2019.+  - The Trans-Omics for Precision Medicine ([[https://​www.nhlbiwgs.org|TOPMed]]) program. The TOPMed Omics [[http://​oncinfo.org/​_media/​wiki:​topmed_omics_survey.pdf|Survey]] in 2017 includes Framingham Heart Study (FHS) details, which are described clearer in [[http://​oncinfo.org/​_media/​wiki:​omics_fhs.pdf|2016]]. [[https://​www.ncbi.nlm.nih.gov/​projects/​gap/​cgi-bin/​molecular.cgi?​study_id=phs000363.v17.p11&​phv=173423&​phd=4119&​pha=&​pht=2941&​phvf=&​phdf=&​phaf=&​phtf=&​dssp=1&​consent=&​temp=1|SABRe]] is a substudy of FHS and has mRNA and miRNA data. We obtained [[https://​docs.google.com/​document/​d/​1B8uKY2QBuJHAiPrv9y_cR9704RrI7nZM71oVc7jt5Q8/​edit|these]] data in 2019. On 2021-04-23, {{:​fhs_multiomics_meeting_msevilla_april21.pdf|Magdalena}} ​ Sevilla presented a collection of FHS and other omics datasets and some methods for analyzing them.
   - Exome Sequencing Project ([[http://​evs.gs.washington.edu|ESP]]),​ richly-phenotyped for heart, lung and blood disorders.   - Exome Sequencing Project ([[http://​evs.gs.washington.edu|ESP]]),​ richly-phenotyped for heart, lung and blood disorders.
   - Alzheimer'​s Disease Sequencing Project ([[https://​www.niagads.org/​adsp/​content/​study-design|ADSP]]),​ WES and WGS of thousands of AD and control samples.   - Alzheimer'​s Disease Sequencing Project ([[https://​www.niagads.org/​adsp/​content/​study-design|ADSP]]),​ WES and WGS of thousands of AD and control samples.
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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.
 +
 +
 +===== Related work =====
 +
 +  - 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.