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A draft map of the human proteome.

Kim MS, Pinto SM, Getnet D, Nirujogi RS, Manda SS, Chaerkady R, Madugundu AK, Kelkar DS, Isserlin R, Jain S, Thomas JK, Muthusamy B, Leal-Rojas P, Kumar P, Sahasrabuddhe NA, Balakrishnan L, Advani J, George B, Renuse S, Selvan LD, Patil AH, Nanjappa V, Radhakrishnan A, Prasad S, Subbannayya T, Raju R, Kumar M, Sreenivasamurthy SK, Marimuthu A, Sathe GJ, Chavan S, Datta KK, Subbannayya Y, Sahu A, Yelamanchi SD, Jayaram S, Rajagopalan P, Sharma J, Murthy KR, Syed N, Goel R, Khan AA, Ahmad S, Dey G, Mudgal K, Chatterjee A, Huang TC, Zhong J, Wu X, Shaw PG, Freed D, Zahari MS, Mukherjee KK, Shankar S, Mahadevan A, Lam H, Mitchell CJ, Shankar SK, Satishchandra P, Schroeder JT, Sirdeshmukh R, Maitra A, Leach SD, Drake CG, Halushka MK, Prasad TS, Hruban RH, Kerr CL, Bader GD, Iacobuzio-Donahue CA, Gowda H, Pandey A - Nature (2014)

Bottom Line: However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet.In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans.A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames.

View Article: PubMed Central - PubMed

Affiliation: 1] McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames. This large human proteome catalogue (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease.

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Isoform-specific expressiona, Exon structure of three known isoforms of FYN (left) along with abundance of isoform-specific peptides detected in the indicated cells/tissues (right). The color key indicates a relative expression based on the spectral counts of isoform-specific peptides detected. b, 20S constitutive proteasome and 20S immunoproteasome core complexes. Expression of their corresponding components are depicted by a heat map (red indicates higher expression) in the Human Proteome Map portal.
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Figure 3: Isoform-specific expressiona, Exon structure of three known isoforms of FYN (left) along with abundance of isoform-specific peptides detected in the indicated cells/tissues (right). The color key indicates a relative expression based on the spectral counts of isoform-specific peptides detected. b, 20S constitutive proteasome and 20S immunoproteasome core complexes. Expression of their corresponding components are depicted by a heat map (red indicates higher expression) in the Human Proteome Map portal.

Mentions: Alternative splicing gives rise to a large number of splice variants at the RNA level, some of which can encode distinct protein isoforms. Multiple protein isoforms are contributed by only one-third of annotated genes, while the remaining two-thirds generate only a single protein product according to the RefSeq database15 (Extended Data Fig. 2d). Although our primary goal was not to obtain complete coverage of splice isoforms, we identified isoform-specific peptides for 2,861 protein isoforms derived from 2,450 genes. For example, we detected isoform 1 of Fyn protein tyrosine kinase in brain and isoform 2 in hematopoietic cells (Fig. 3a). This is significant because although we did not detect the third known isoform of FYN, the two isoforms that we identified are known to possess distinct functional properties.


A draft map of the human proteome.

Kim MS, Pinto SM, Getnet D, Nirujogi RS, Manda SS, Chaerkady R, Madugundu AK, Kelkar DS, Isserlin R, Jain S, Thomas JK, Muthusamy B, Leal-Rojas P, Kumar P, Sahasrabuddhe NA, Balakrishnan L, Advani J, George B, Renuse S, Selvan LD, Patil AH, Nanjappa V, Radhakrishnan A, Prasad S, Subbannayya T, Raju R, Kumar M, Sreenivasamurthy SK, Marimuthu A, Sathe GJ, Chavan S, Datta KK, Subbannayya Y, Sahu A, Yelamanchi SD, Jayaram S, Rajagopalan P, Sharma J, Murthy KR, Syed N, Goel R, Khan AA, Ahmad S, Dey G, Mudgal K, Chatterjee A, Huang TC, Zhong J, Wu X, Shaw PG, Freed D, Zahari MS, Mukherjee KK, Shankar S, Mahadevan A, Lam H, Mitchell CJ, Shankar SK, Satishchandra P, Schroeder JT, Sirdeshmukh R, Maitra A, Leach SD, Drake CG, Halushka MK, Prasad TS, Hruban RH, Kerr CL, Bader GD, Iacobuzio-Donahue CA, Gowda H, Pandey A - Nature (2014)

Isoform-specific expressiona, Exon structure of three known isoforms of FYN (left) along with abundance of isoform-specific peptides detected in the indicated cells/tissues (right). The color key indicates a relative expression based on the spectral counts of isoform-specific peptides detected. b, 20S constitutive proteasome and 20S immunoproteasome core complexes. Expression of their corresponding components are depicted by a heat map (red indicates higher expression) in the Human Proteome Map portal.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403737&req=5

Figure 3: Isoform-specific expressiona, Exon structure of three known isoforms of FYN (left) along with abundance of isoform-specific peptides detected in the indicated cells/tissues (right). The color key indicates a relative expression based on the spectral counts of isoform-specific peptides detected. b, 20S constitutive proteasome and 20S immunoproteasome core complexes. Expression of their corresponding components are depicted by a heat map (red indicates higher expression) in the Human Proteome Map portal.
Mentions: Alternative splicing gives rise to a large number of splice variants at the RNA level, some of which can encode distinct protein isoforms. Multiple protein isoforms are contributed by only one-third of annotated genes, while the remaining two-thirds generate only a single protein product according to the RefSeq database15 (Extended Data Fig. 2d). Although our primary goal was not to obtain complete coverage of splice isoforms, we identified isoform-specific peptides for 2,861 protein isoforms derived from 2,450 genes. For example, we detected isoform 1 of Fyn protein tyrosine kinase in brain and isoform 2 in hematopoietic cells (Fig. 3a). This is significant because although we did not detect the third known isoform of FYN, the two isoforms that we identified are known to possess distinct functional properties.

Bottom Line: However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet.In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans.A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames.

View Article: PubMed Central - PubMed

Affiliation: 1] McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames. This large human proteome catalogue (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease.

Show MeSH
Related in: MedlinePlus