Placenta Rectum Endometrium Smooth muscle Bone marrow Testis Tonsil Pituitary Kidney Duodenum Ovary Appendix Spleen Gallbladder Heart muscle Lymph node Thyroid gland Salivary gland Fallopian tube Colon Esophagus Lung Pancreas Small intestine Stomach Adrenal gland Cerebellum Cerebrum Liver Breast Prostate Cervix Urinary bladder Vagina Skeletal muscle Blood Artery Adipose tissue Skin Nerve FANTOM HPA GTEx FANTOM HPA GTEx Genes expressed in all tissues 8385 Expression not detected 1021 Expression enriched in tissue 2359 Group enriched expression 1208 Enhanced expression 3227 Mixed expression 2484 45% 13% HPA A To explore the human proteome in more depth, visit www.proteinatlas.org Modified from: Uhlén M, Hallström BM, Lindskog C, Mardinoglu A, Pontén F, Nielsen J (2016). Mol Syst Biol. 12(4): 862 msb.embopress.org /content/12/4/862 Human transcriptome resources Several genome-wide transcriptome profiling methods have been used for quantifying global gene expression patterns. Some of these publicly available repositories for transcriptomics data are summarized in the table of QR codes with a focus on datasets from RNA-seq experiments. The resources include repositories for external data, such as Expression Atlas from the European Bioinformatics Institute (EBI) and Gene Expression Omnibus from the National Center for Biotechnology Information (NCBI), as well as repositories with internally generated transcriptome data, such as the GTEx, the Human Protein Atlas, and the Allen Brain Atlas. Global transcriptomics analysis of human tissues and organs Overview of the tissues and organs analyzed using RNA-seq by the Human Protein Atlas consortium (HPA, dark red), using cap analysis gene expression (CAGE) by the FANTOM consortium (light red), and using RNA-seq by the genome-based tissue expression consortium (GTEx, pink). Altogether, 22 tissues and organs were studied by both the HPA and FANTOM, while 21 tissues overlapped between the HPA and GTEx datasets. Classification of all human genes based on tissue expression A | The classification of the human protein-coding transcriptome shows that almost half of the genes are detected in all tissues, while 13% show a mixed expression. The number of tissue- enriched genes in the different tissues and the overlap between the Human Protein Atlas consortium (HPA) and the genome-based tissue expression consortium (GTEx) are shown in B. Overall, it is reassuring that there is a significant overlap in the tissue classification of the genes based on the two independent datasets. The fact that similar results are obtained when using fresh frozen tissue (HPA) and postmortem tissue (GTEx) suggests negligible effects of the sampling procedures used by the GTEx consortium on RNA degradation. Testis Brain Fallopian tube Small intestine Adipose tissue Lung Colon Ovary Spleen Stomach Heart Esophagus Kidney Pancreas Liver Skin Skeletal muscle Adrenal gland Thyroid Prostate B A B Recon1 2007 2010 2013 2014 EHMN HepatoNet iAdipocytes Recon2 HMR2 0 1500 3000 4500 6000 7500 9000 Genes Metabolites Reactions HPA GTEx RNA-Seq Atlas J. Gutenberg University (Germany) A reference database for gene expression profiling in normal tissue by next-generation sequencing KRUPP et al, 2012 medicalgenomics.org/rna_seq_atlas ArrayExpress The European Bioinformatics Institute EMBL-EBI (UK) International functional genomics public data repositories RUSTICI et al, 2013 www.ebi.ac.uk/arrayexpress FANTOM Riken Institute (Japan) Tissue-based RNA data based on CAGE YU et al, 2015 fantom.gsc.riken.jp Expression Atlas The European Bioinformatics Institute EMBL-EBI (UK) Repository for RNA expression data (both microarray and RNA-seq) PETRYSZAK et al, 2015 www.ebi.ac.uk/gxa GTEx Broad Institute (USA) Tissue-based RNA data based on post mortem samples (RNA-seq) KEEN & MOORE, 2015 www.gtexportal.org Human Protein Atlas KTH Royal Institute of Technology (Sweden) Tissue-based RNA data based on surgically removed tissues (RNA-seq) UHLÉN et al, 2015 www.proteinatlas.org Scan the QR code with a mobile device to visit the web sites. Allen Brain Atlas Allen Institute (USA) An anatomically comprehensive atlas of the adult human brain transcriptome HAWRYLYCZ et al, 2012 human.brain-map.org Gene Expression Omnibus National Center for Biotechnology Information NCBI (USA) Repository for RNA expression data (both microarray and RNA-seq) BARRETT et al, 2013 www.ncbi.nlm.nih.gov/geo Proteomics Transcriptomics Metabolomics 32 Tissues & Organs HPA RNA-seq 22 Tissues & Organs FANTOM CAGE 29 Tissues & Organs GTEx RNA-seq 21 16 16 22 Genome-scale metabolic models for human cells and tissues A | Proteomics and transcriptomics data can be used for generating and improving context- specific biological networks including protein– protein interaction, regulatory, signaling, and metabolic networks in order to gain further insights into the differences in cellular functions across tissues. Genome-scale metabolic models (GEMs) that can be reconstructed directly from proteomics or transcriptomics data are particularly well suited for analyzing biological functions, since they can be applied to examine the metabolic functions associated with a given cell type. B | Timeline of selected human genomic-scale cell-/tissue-specific metabolic models. HMR2 is currently the most comprehensive global reconstruction of human metabolism and this model together with other models of human metabolism has served as a basis for the reconstruction of context-specific GEMs. ROYAL INSTITUTE OF TECHNOLOGY AltIso Massachusetts Institute of Technology MIT (USA) Alternative isoform regulation in human tissue transcriptomes WANG et al, 2008 www.ncbi.nlm.nih.gov/geo /query/acc.cgi?acc=GSE12946 Evolution of gene expression University of Lausanne (Switzerland) The evolution of gene expression levels in mammalian organs BRAWAND et al, 2011 www.ncbi.nlm.nih.gov/geo /query/acc.cgi?acc=GSE30352 Illumina Body Map Illumina (USA) RNA-seq of 16 human individual tissues RUSTICI et al, 2013 www.ebi.ac.uk/arrayexpress /experiments/E-MTAB-513 THE HUMAN TRANSCRIPTOME The human genome consists of DNA, a molecule that contains the instructions needed to build and maintain cells. These instructions are spelled out in the form of four "base pairs”, organized into approximately 20,000 protein-coding genes. For the instructions to be carried out, DNA must be "read" and transcribed into RNA transcripts. The transcriptome is a collection of all the transcripts present in a cell. Here, we focus on the protein-coding transcriptome to explore when and where each transcript and the corresponding protein is present in the various cells. © 2016 EMBO Press | Coordination by SciLifeLab: T. Alm and F. Henningson Johnson | Concept by M. Uhlén, B.M. Hallström, C. Lindskog, A. Mardinoglu, F. Pontén and J. Nielsen | Illustrations: Molecular Systems Biology ( U. Mackensen) The central dogma in molecular biology The central dogma of molecular biology explains that DNA codes for RNA, which codes for proteins. DNA is the molecule of heredity that passes from parents to offspring. It contains the instructions for building RNA and proteins, which make up the structure of the body and carry out most of its functions. Protein PROTEOME A R N D C E Q G H I L K M F P S T W Y V AMINO ACIDS TRANSLATION POLYPEPTIDE TRANSCRIPTOME RNA A U C G NUCLEOBASES mRNA tRNA DNA TRANSCRIPTION GENOME RNA TRANSCRIPT A T C G NUCLEOBASES
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PlacentaRectum
EndometriumSmooth muscle
Bone marrowTestis
TonsilPituitary
KidneyDuodenum
OvaryAppendix
SpleenGallbladder
Heart muscleLymph node
Thyroid glandSalivary gland
Fallopian tubeColon
EsophagusLung
PancreasSmall intestine
StomachAdrenal gland
CerebellumCerebrum
Liver Breast
Prostate Cervix
Urinary bladder Vagina
Skeletal muscle Blood
ArteryAdipose tissue
Skin Nerve
FAN
TOM
HPA
GTE
x
FAN
TOM
HPA
GTE
x
Genes expressed inall tissues8385
Expressionnot detected1021
Expressionenriched in tissue2359
Group enriched expression1208
Enhancedexpression3227
Mixedexpression2484
45%
13%
HPAA
To explore the human proteome in more depth, visit
www.proteinatlas.org
Modified from: Uhlén M, Hallström BM, Lindskog C, Mardinoglu A, Pontén F, Nielsen J (2016).
Mol Syst Biol. 12(4): 862
msb.embopress.org /content/12/4/862
Human transcriptomeresourcesSeveral genome-wide transcriptome profiling methods have been used for quantifying global gene expression patterns. Some of these publicly available repositories for transcriptomics data are summarized in the table of QR codes with a focus on datasets from RNA-seq experiments. The resources include repositories for external data, such as Expression Atlas from the European Bioinformatics Institute (EBI) and Gene Expression Omnibus from the National Center for Biotechnology Information (NCBI), as well as repositories with internally generated transcriptome data, such as the GTEx, the Human Protein Atlas, and the Allen Brain Atlas.
Global transcriptomics analysis of human tissues and organsOverview of the tissues and organs analyzed using RNA-seq by the Human Protein Atlas consortium (HPA, dark red), using cap analysis gene expression (CAGE) by the FANTOM consortium (light red), and using RNA-seq by the genome-based tissue expression consortium (GTEx, pink). Altogether, 22 tissues and organs were studied by both the HPA and FANTOM, while 21 tissues overlapped between the HPA and GTEx datasets.
Classification of all human genes based on tissue expressionA| The classification of the human protein-coding transcriptome shows that almost half of the genes are detected in all tissues, while 13% show a mixed expression. The number of tissue-enriched genes in the different tissues and the overlap between the Human Protein Atlas consortium (HPA) and the genome-based tissue expression consortium (GTEx) are shown in B. Overall, it is reassuring that there is a significant overlap in the tissue classification of the genes based on the two independent datasets. The fact that similar results are obtained when using fresh frozen tissue (HPA) and postmortem tissue (GTEx) suggests negligible effects of the sampling procedures used by the GTEx consortium on RNA degradation.
Testis
BrainFallopian
tubeSmall
intestine Adiposetissue
Lung
Colon
Ovary
SpleenStomach
HeartEsophagus
KidneyPancreas
Liver
Skin
Skeletalmuscle
Adrenalgland
Thyroid
Prostate
B
A
B Recon12007
2010
2013
2014
EHMN
HepatoNet
iAdipocytes
Recon2
HMR2
0 1500 3000 4500 6000 7500 9000
Genes
MetabolitesReactions
HPAGTEx
RNA-Seq AtlasJ. Gutenberg University (Germany)A reference database for gene expression profiling in normal tissue by next-generation sequencingKRUPP et al, 2012
medicalgenomics.org/rna_seq_atlas
ArrayExpressThe European Bioinformatics InstituteEMBL-EBI (UK)International functional genomics public data repositoriesRUSTICI et al, 2013
www.ebi.ac.uk/arrayexpress
FANTOMRiken Institute (Japan)Tissue-based RNA data based on CAGEYU et al, 2015
fantom.gsc.riken.jp
Expression AtlasThe European Bioinformatics InstituteEMBL-EBI (UK)Repository for RNA expression data(both microarray and RNA-seq)PETRYSZAK et al, 2015
www.ebi.ac.uk/gxa
GTExBroad Institute (USA)Tissue-based RNA data based on post mortem samples (RNA-seq)KEEN & MOORE, 2015
www.gtexportal.org
Human Protein AtlasKTH Royal Institute of Technology(Sweden)Tissue-based RNA data based on surgically removed tissues (RNA-seq)UHLÉN et al, 2015
www.proteinatlas.org
Scan the QR code with a mobile device to visit the web sites.
Allen Brain AtlasAllen Institute (USA)An anatomically comprehensive atlas of the adult human brain transcriptomeHAWRYLYCZ et al, 2012
human.brain-map.org
Gene Expression OmnibusNational Center for Biotechnology InformationNCBI (USA)Repository for RNA expression data(both microarray and RNA-seq)BARRETT et al, 2013
www.ncbi.nlm.nih.gov/geo
Proteomics
Transcriptomics
Metabolomics
32Tissues & Organs
HPARNA-seq
22Tissues & OrgansFANTOMCAGE
29Tissues &
OrgansGTEx
RNA-seq
21
16
1622
Genome-scale metabolic models for human cells and tissuesA| Proteomics and transcriptomics data can be used for generating and improving context-specific biological networks including protein–protein interaction, regulatory, signaling, and metabolic networks in order to gain further insights into the differences in cellular functions across tissues. Genome-scale metabolic models (GEMs) that can be reconstructed directly from proteomics or transcriptomics data are particularly well suited for analyzing biological functions, since they can be applied to examine the metabolic functions associated with a given cell type.B| Timeline of selected human genomic-scale cell-/tissue-specific metabolic models. HMR2 is currently the most comprehensive global reconstruction of human metabolism and this model together with other models of human metabolism has served as a basis for the reconstruction of context-specific GEMs.
ROYAL INSTITUTE OF TECHNOLOGY
AltIsoMassachusetts Institute of TechnologyMIT (USA)Alternative isoform regulation in human tissue transcriptomesWANG et al, 2008
www.ncbi.nlm.nih.gov/geo /query/acc.cgi?acc=GSE12946
Evolution of gene expressionUniversity of Lausanne (Switzerland)The evolution of gene expression levels in mammalian organsBRAWAND et al, 2011
www.ncbi.nlm.nih.gov/geo /query/acc.cgi?acc=GSE30352
Illumina Body MapIllumina (USA)RNA-seq of 16 human individual tissuesRUSTICI et al, 2013
www.ebi.ac.uk/arrayexpress /experiments/E-MTAB-513
THE HUMAN TRANSCRIPTOMEThe human genome consists of DNA, a molecule that contains the instructions needed to build and maintain cells. These instructions are spelled out in the form of four "base pairs”,
organized into approximately 20,000 protein-coding genes. For the instructions to be carried out, DNA must be "read" and transcribed into RNA transcripts. The transcriptome is a collection of all the transcripts present in a cell. Here, we focus on the protein-coding transcriptome to explore when and where each transcript and
the corresponding protein is present in the various cells.
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The central dogma in molecular biologyThe central dogma of molecular biology explains that DNA codes for RNA, which codes for proteins. DNA is the molecule of heredity that passes from parents to offspring. It contains the instructions for building RNA and proteins, which make up the structure of the body and carry out most of its functions.
Protein PROTEOMEA R N D C E Q G H IL K M F PS T W Y V
AMINO ACIDS
TRANSLATIONPOLYPEPTIDE
TRANSCRIPTOMERNA A U C GNUCLEOBASES
mRNAtRNA
DNA
TRANSCRIPTION
GENOME
RNATRANSCRIPT
A T C G
NUCLEOBASES
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