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multiomics_analysis_for_dementia [2019/06/07 17:55]
admin [Related work]
multiomics_analysis_for_dementia [2020/04/15 21:21] (current)
admin [Related work]
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 ===== Data ===== ===== Data =====
  
-Large cohorts with phenotype data on dementia are available through:+Large cohorts with phenotype data on dementia are available through ​the following resources (incomplete [[https://​docs.google.com/​spreadsheets/​d/​1NpWRjxwwCJp-AKci239fjCf2IDg-oJONdNAuBojsG9I/​edit#​gid=305034359|table]] of data types):
  
   - 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.+  - 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.
   - 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.
   - Allen Brain [[http://​portal.brain-map.org/​|Atlases]] has many different [[http://​aging.brain-map.org/​overview/​home|downloadable]] data types, but from a few mouse and human samples. RNA-Seq data of hundreds of dementia cases.   - Allen Brain [[http://​portal.brain-map.org/​|Atlases]] has many different [[http://​aging.brain-map.org/​overview/​home|downloadable]] data types, but from a few mouse and human samples. RNA-Seq data of hundreds of dementia cases.
-  - The Alzheimer'​s Disease Neuroimaging Initiative ([[http://​adni.loni.usc.edu/​data-samples/​data-types/​|ADNI]]) has genetic and imaging data of 1-3 K samples. 
   - The Image and Data Archive ([[https://​ida.loni.usc.edu|IDA]]) contains mostly image data on 43,290 subjects from 119 studies.   - The Image and Data Archive ([[https://​ida.loni.usc.edu|IDA]]) contains mostly image data on 43,290 subjects from 119 studies.
 +  - The Alzheimer'​s Disease Neuroimaging Initiative ([[http://​adni.loni.usc.edu/​data-samples/​data-types/​|ADNI]]) has genetic and imaging data of 1-3 K samples, which are available through [[https://​ida.loni.usc.edu|IDA]].
   - Several studies share their data through Accelerating Medicines Partnership - Alzheimer'​s Disease ([[https://​www.synapse.org/#​!Synapse:​syn5550382|AMP-AD]]) including:   - Several studies share their data through Accelerating Medicines Partnership - Alzheimer'​s Disease ([[https://​www.synapse.org/#​!Synapse:​syn5550382|AMP-AD]]) including:
       - The Adult Changes in Thought ([[https://​www.synapse.org/#​!Synapse:​syn5759376|ACT]]) measured ~4K __proteins__ ​ in ~50 brains and performed WGCNA. Also, proteome data in BLSA (~100 brains), Banner (~200), and UPPpilot (~200).       - The Adult Changes in Thought ([[https://​www.synapse.org/#​!Synapse:​syn5759376|ACT]]) measured ~4K __proteins__ ​ in ~50 brains and performed WGCNA. Also, proteome data in BLSA (~100 brains), Banner (~200), and UPPpilot (~200).
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       - The Mount Sinai Brain Bank ([[https://​www.synapse.org/#​!Synapse:​syn3159438|MSBB]]) includes proteome and gene expression profiles from hundreds of samples.       - The Mount Sinai Brain Bank ([[https://​www.synapse.org/#​!Synapse:​syn3159438|MSBB]]) includes proteome and gene expression profiles from hundreds of samples.
       - The [[https://​www.synapse.org/#​!Synapse:​syn5550404|MayoRNAseq]] includes WGS and RNA-Seq data from 275 Cerebellum (CBE) and 276 Temporal cortex (TCX) samples.       - The [[https://​www.synapse.org/#​!Synapse:​syn5550404|MayoRNAseq]] includes WGS and RNA-Seq data from 275 Cerebellum (CBE) and 276 Temporal cortex (TCX) samples.
-  - The Religious Orders Study and Memory and Aging Project ([[https://​www.synapse.org/#​!Synapse:​syn3219045|ROSMAP]]) is the **richest** ​ dataset in AMP-AD in terms of variety of data types, which include gene expression, genome, proteome, metabolome, and image data. Also, DNA methylation,​ miRNA, WGS, WES, and even H3K9Ac are available for ~1K samples. The dataset is very well [[https://​www.radc.rush.edu/​docs/​omics.htm|documented]].+  - The Religious Orders Study and Memory and Aging Project ([[https://​www.synapse.org/#​!Synapse:​syn3219045|ROSMAP]]) is the **richest** ​ dataset in AMP-AD in terms of variety of data types, which include gene expression, genome, proteome, metabolome, and image data. Also, DNA methylation,​ miRNA, WGS, WES, and even H3K9Ac are available for ~1K samples. The dataset is very well [[https://​www.radc.rush.edu/​docs/​omics.htm|documented]], and was used to identify [[http://​mostafavilab.stat.ubc.ca/​xqtl/​|xQTL]] by Philip De Jager. 
 +  - Mathys, Hansruedi, et al. "​**Single-cell** ​ transcriptomic analysis of Alzheimer’s disease."​ Nature ([[https://​www.nature.com/​articles/​s41586-019-1195-2|2019]]). \\  Radek'​s summary: "​Showing ~80K single cell transcriptomic analysis on brain tissues from ~50 patients with Alzheimer'​s disease. Subpopulations of glia and neurons expressed different gene signatures associated with AD. These enormous cataloging data may help to further pinpoint pathways associated with AD.", and his [[:plan|]]. Habil'​s [[https://​docs.google.com/​presentation/​d/​1u2rv9FExW44JfJsqPjenJcCsCFnOSUbJUxQwalviNHk/​edit#​slide=id.p|presentation]] in Biggs journal club on 2 July 2019. 
 +  - 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.
  
  
 ===== 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, ​and [[https://​biggsinstitute.org/​team-member/​claudia-l-satizabal-phd/​|Dr. Claudia Satizabal]].+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]]. 
  
 ===== Subprojects ===== ===== Subprojects =====
  
-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. 
  
 ===== Related work ===== ===== Related work =====
  
-  - 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]]. 
-  - MathysHansruedi, et al. "Single-cell transcriptomic analysis ​of Alzheimer’s disease." ​Nature ([[https://​www.nature.com/​articles/​s41586-019-1195-2|2019]]). \\  Radek'​s summary: "​Showing single cell transcriptomic analysis on brain tissues from ~50 patients with Alzheimer'​s ​disease. Subpopulations of glia and neurons expressed different gene signatures associated with ADThese enormous cataloging data may help to further pinpoint pathways associated with AD.", and his {{:wiki:img_20190516_162440263.jpg?​linkonly|plan}}.+  - SatizabalClaudia L., et al. "Genetic architecture ​of subcortical brain structures in over 40,000 individuals worldwide."​ [[https://​www.biorxiv.org/​content/​10.1101/​173831v1.full|bioRxiv]] (2017): 173831. \\  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.