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1. An atlas of healthy and injured cell states and niches in the human kidney.

Author

Lake, Blue, Lake, Blue, Menon, Rajasree, Winfree, Seth, Hu, Qiwen, Ferreira, Ricardo, Kalhor, Kian, Barwinska, Daria, Otto, Edgar, Ferkowicz, Michael, Diep, Dinh, Plongthongkum, Nongluk, Knoten, Amanda, Urata, Sarah, Mariani, Laura, Naik, Abhijit, Eddy, Sean, Zhang, Bo, Wu, Yan, Salamon, Diane, Williams, James, Wang, Xin, Balderrama, Karol, Hoover, Paul, Murray, Evan, Marshall, Jamie, Noel, Teia, Vijayan, Anitha, Hartman, Austin, Chen, Fei, Waikar, Sushrut, Rosas, Sylvia, Wilson, Francis, Palevsky, Paul, Kiryluk, Krzysztof, Sedor, John, Toto, Robert, Parikh, Chirag, Kim, Eric, Satija, Rahul, Greka, Anna, Macosko, Evan, Kharchenko, Peter, Gaut, Joseph, Hodgin, Jeffrey, Eadon, Michael, Dagher, Pierre, El-Achkar, Tarek, Kretzler, Matthias, Jain, Sanjay, Zhang, Kun, Lake, Blue, Lake, Blue, Menon, Rajasree, Winfree, Seth, Hu, Qiwen, Ferreira, Ricardo, Kalhor, Kian, Barwinska, Daria, Otto, Edgar, Ferkowicz, Michael, Diep, Dinh, Plongthongkum, Nongluk, Knoten, Amanda, Urata, Sarah, Mariani, Laura, Naik, Abhijit, Eddy, Sean, Zhang, Bo, Wu, Yan, Salamon, Diane, Williams, James, Wang, Xin, Balderrama, Karol, Hoover, Paul, Murray, Evan, Marshall, Jamie, Noel, Teia, Vijayan, Anitha, Hartman, Austin, Chen, Fei, Waikar, Sushrut, Rosas, Sylvia, Wilson, Francis, Palevsky, Paul, Kiryluk, Krzysztof, Sedor, John, Toto, Robert, Parikh, Chirag, Kim, Eric, Satija, Rahul, Greka, Anna, Macosko, Evan, Kharchenko, Peter, Gaut, Joseph, Hodgin, Jeffrey, Eadon, Michael, Dagher, Pierre, El-Achkar, Tarek, Kretzler, Matthias, Jain, Sanjay, and Zhang, Kun more...

Abstract

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations. more...

Published
2023

2. A reference tissue atlas for the human kidney.

Author

Hansen, Jens, Hansen, Jens, Sealfon, Rachel, Menon, Rajasree, Eadon, Michael T, Lake, Blue B, Steck, Becky, Anjani, Kavya, Parikh, Samir, Sigdel, Tara K, Zhang, Guanshi, Velickovic, Dusan, Barwinska, Daria, Alexandrov, Theodore, Dobi, Dejan, Rashmi, Priyanka, Otto, Edgar A, Rivera, Miguel, Rose, Michael P, Anderton, Christopher R, Shapiro, John P, Pamreddy, Annapurna, Winfree, Seth, Xiong, Yuguang, He, Yongqun, de Boer, Ian H, Hodgin, Jeffrey B, Barisoni, Laura, Naik, Abhijit S, Sharma, Kumar, Sarwal, Minnie M, Zhang, Kun, Himmelfarb, Jonathan, Rovin, Brad, El-Achkar, Tarek M, Laszik, Zoltan, He, John Cijiang, Dagher, Pierre C, Valerius, M Todd, Jain, Sanjay, Satlin, Lisa M, Troyanskaya, Olga G, Kretzler, Matthias, Iyengar, Ravi, Azeloglu, Evren U, Kidney Precision Medicine Project, Hansen, Jens, Hansen, Jens, Sealfon, Rachel, Menon, Rajasree, Eadon, Michael T, Lake, Blue B, Steck, Becky, Anjani, Kavya, Parikh, Samir, Sigdel, Tara K, Zhang, Guanshi, Velickovic, Dusan, Barwinska, Daria, Alexandrov, Theodore, Dobi, Dejan, Rashmi, Priyanka, Otto, Edgar A, Rivera, Miguel, Rose, Michael P, Anderton, Christopher R, Shapiro, John P, Pamreddy, Annapurna, Winfree, Seth, Xiong, Yuguang, He, Yongqun, de Boer, Ian H, Hodgin, Jeffrey B, Barisoni, Laura, Naik, Abhijit S, Sharma, Kumar, Sarwal, Minnie M, Zhang, Kun, Himmelfarb, Jonathan, Rovin, Brad, El-Achkar, Tarek M, Laszik, Zoltan, He, John Cijiang, Dagher, Pierre C, Valerius, M Todd, Jain, Sanjay, Satlin, Lisa M, Troyanskaya, Olga G, Kretzler, Matthias, Iyengar, Ravi, Azeloglu, Evren U, and Kidney Precision Medicine Project more...

Abstract

Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of the kidney following its physiological functions and link cell subtypes to genes, proteins, metabolites, and pathways. They further show that messenger RNA levels along the nephron are congruent with the subsegmental physiological activity. This reference atlas provides a framework for the classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes. more...

Published
2022

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3. A reference tissue atlas for the human kidney.

Author

Hansen, Jens, Hansen, Jens, Sealfon, Rachel, Menon, Rajasree, Eadon, Michael T, Lake, Blue B, Steck, Becky, Anjani, Kavya, Parikh, Samir, Sigdel, Tara K, Zhang, Guanshi, Velickovic, Dusan, Barwinska, Daria, Alexandrov, Theodore, Dobi, Dejan, Rashmi, Priyanka, Otto, Edgar A, Rivera, Miguel, Rose, Michael P, Anderton, Christopher R, Shapiro, John P, Pamreddy, Annapurna, Winfree, Seth, Xiong, Yuguang, He, Yongqun, de Boer, Ian H, Hodgin, Jeffrey B, Barisoni, Laura, Naik, Abhijit S, Sharma, Kumar, Sarwal, Minnie M, Zhang, Kun, Himmelfarb, Jonathan, Rovin, Brad, El-Achkar, Tarek M, Laszik, Zoltan, He, John Cijiang, Dagher, Pierre C, Valerius, M Todd, Jain, Sanjay, Satlin, Lisa M, Troyanskaya, Olga G, Kretzler, Matthias, Iyengar, Ravi, Azeloglu, Evren U, Kidney Precision Medicine Project, Hansen, Jens, Hansen, Jens, Sealfon, Rachel, Menon, Rajasree, Eadon, Michael T, Lake, Blue B, Steck, Becky, Anjani, Kavya, Parikh, Samir, Sigdel, Tara K, Zhang, Guanshi, Velickovic, Dusan, Barwinska, Daria, Alexandrov, Theodore, Dobi, Dejan, Rashmi, Priyanka, Otto, Edgar A, Rivera, Miguel, Rose, Michael P, Anderton, Christopher R, Shapiro, John P, Pamreddy, Annapurna, Winfree, Seth, Xiong, Yuguang, He, Yongqun, de Boer, Ian H, Hodgin, Jeffrey B, Barisoni, Laura, Naik, Abhijit S, Sharma, Kumar, Sarwal, Minnie M, Zhang, Kun, Himmelfarb, Jonathan, Rovin, Brad, El-Achkar, Tarek M, Laszik, Zoltan, He, John Cijiang, Dagher, Pierre C, Valerius, M Todd, Jain, Sanjay, Satlin, Lisa M, Troyanskaya, Olga G, Kretzler, Matthias, Iyengar, Ravi, Azeloglu, Evren U, and Kidney Precision Medicine Project more...

Abstract

Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of the kidney following its physiological functions and link cell subtypes to genes, proteins, metabolites, and pathways. They further show that messenger RNA levels along the nephron are congruent with the subsegmental physiological activity. This reference atlas provides a framework for the classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes. more...

Published
2022

4. Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen

Author

Salem, Rany M., Todd, Jennifer N., Sandholm, Niina, Cole, Joanne B., Chen, Wei-Min, Andrews, Darrell, Pezzolesi, Marcus G., McKeigue, Paul M., Hiraki, Linda T., Qiu, Chengxiang, Nair, Viji, Di Liao, Chen, Cao, Jing Jing, Valo, Erkka, Onengut-Gumuscu, Suna, Smiles, Adam M., McGurnaghan, Stuart J., Haukka, Jani K., Harjutsalo, Valma, Brennan, Eoin P., van Zuydam, Natalie, Ahlqvist, Emma, Doyle, Ross, Ahluwalia, Tarunveer S., Lajer, Maria, Hughes, Maria F., Park, Jihwan, Skupien, Jan, Spiliopoulou, Athina, Liu, Andrew, Menon, Rajasree, Boustany-Kari, Carine M., Kang, Hyun M., Nelson, Robert G., Klein, Ronald, Klein, Barbara E., Lee, Kristine E., Gao, Xiaoyu, Mauer, Michael, Maestroni, Silvia, Caramori, Maria Luiza, de Boer, Ian H., Miller, Rachel G., Guo, Jingchuan, Boright, Andrew P., Tregouet, David, Gyorgy, Beata, Snell-Bergeon, Janet K., Maahs, David M., Bull, Shelley B., Canty, Angelo J., Palmer, Colin N. A., Stechemesser, Lars, Paulweber, Bernhard, Weitgasser, Raimund, Sokolovska, Jelizaveta, Rovite, Vita, Pirags, Valdis, Prakapiene, Edita, Radzeviciene, Lina, Verkauskiene, Rasa, Panduru, Nicolae Mircea, Groop, Leif C., McCarthy, Mark, I, Gu, Harvest F., Möllsten, Anna, Falhammar, Henrik, Brismar, Kerstin, Martin, Finian, Rossing, Peter, Costacou, Tina, Zerbini, Gianpaolo, Marre, Michel, Hadjadj, Samy, McKnight, Amy J., Forsblom, Carol, McKay, Gareth, Godson, Catherine, Maxwell, A. Peter, Kretzler, Matthias, Susztak, Katalin, Colhoun, Helen M., Krolewski, Andrzej, Paterson, Andrew D., Groop, Per-Henrik, Rich, Stephen S., Hirschhorn, Joel N., Florez, Jose C., Salem, Rany M., Todd, Jennifer N., Sandholm, Niina, Cole, Joanne B., Chen, Wei-Min, Andrews, Darrell, Pezzolesi, Marcus G., McKeigue, Paul M., Hiraki, Linda T., Qiu, Chengxiang, Nair, Viji, Di Liao, Chen, Cao, Jing Jing, Valo, Erkka, Onengut-Gumuscu, Suna, Smiles, Adam M., McGurnaghan, Stuart J., Haukka, Jani K., Harjutsalo, Valma, Brennan, Eoin P., van Zuydam, Natalie, Ahlqvist, Emma, Doyle, Ross, Ahluwalia, Tarunveer S., Lajer, Maria, Hughes, Maria F., Park, Jihwan, Skupien, Jan, Spiliopoulou, Athina, Liu, Andrew, Menon, Rajasree, Boustany-Kari, Carine M., Kang, Hyun M., Nelson, Robert G., Klein, Ronald, Klein, Barbara E., Lee, Kristine E., Gao, Xiaoyu, Mauer, Michael, Maestroni, Silvia, Caramori, Maria Luiza, de Boer, Ian H., Miller, Rachel G., Guo, Jingchuan, Boright, Andrew P., Tregouet, David, Gyorgy, Beata, Snell-Bergeon, Janet K., Maahs, David M., Bull, Shelley B., Canty, Angelo J., Palmer, Colin N. A., Stechemesser, Lars, Paulweber, Bernhard, Weitgasser, Raimund, Sokolovska, Jelizaveta, Rovite, Vita, Pirags, Valdis, Prakapiene, Edita, Radzeviciene, Lina, Verkauskiene, Rasa, Panduru, Nicolae Mircea, Groop, Leif C., McCarthy, Mark, I, Gu, Harvest F., Möllsten, Anna, Falhammar, Henrik, Brismar, Kerstin, Martin, Finian, Rossing, Peter, Costacou, Tina, Zerbini, Gianpaolo, Marre, Michel, Hadjadj, Samy, McKnight, Amy J., Forsblom, Carol, McKay, Gareth, Godson, Catherine, Maxwell, A. Peter, Kretzler, Matthias, Susztak, Katalin, Colhoun, Helen M., Krolewski, Andrzej, Paterson, Andrew D., Groop, Per-Henrik, Rich, Stephen S., Hirschhorn, Joel N., and Florez, Jose C. more...

Abstract

Background: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown. Methods: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function. Results: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition (BMP7) or renal biology (COLEC11 and DDR1). Conclusions: The 16 diabetic kidney disease–associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment. more...

Published
2019
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5. Quest for Missing Proteins : Update 2015 on Chromosome-Centric Human Proteome Project

Author

Horvatovich, Peter, Lundberg, Emma K., Chen, Yu-Ju, Sung, Ting-Yi, He, Fuchu, Nice, Edouard C., Goode, Robert J., Yu, Simon, Ranganathan, Shoba, Baker, Mark S., Domont, Gilberto B., Velasquez, Erika, Li, Dong, Liu, Siqi, Wang, Quanhui, He, Qing-Yu, Menon, Rajasree, Guan, Yuanfang, Corrales, Fernando J., Segura, Victor, Casal, J. Ignacio, Pascual-Montano, Alberto, Albar, Juan P., Fuentes, Manuel, Gonzalez-Gonzalez, Maria, Diez, Paula, Ibarrola, Nieves, Degano, Rosa M., Mohammed, Yassene, Borchers, Christoph H., Urbani, Andrea, Soggiu, Alessio, Yamamoto, Tadashi, Salekdeh, Ghasem Hosseini, Archakov, Alexander, Ponomarenko, Elena, Lisitsa, Andrey, Lichti, Cheryl F., Mostovenko, Ekaterina, Kroes, Roger A., Rezeli, Melinda, Vegvari, Akos, Fehniger, Thomas E., Bischoff, Rainer, Vizcaino, Juan Antonio, Deutsch, Eric W., Lane, Lydie, Nilsson, Carol L., Marko-Varga, Gyorgy, Omenn, Gilbert S., Jeong, Seul-Ki, Lim, Jong-Sun, Paik, Young-Ki, Hancock, William S., Horvatovich, Peter, Lundberg, Emma K., Chen, Yu-Ju, Sung, Ting-Yi, He, Fuchu, Nice, Edouard C., Goode, Robert J., Yu, Simon, Ranganathan, Shoba, Baker, Mark S., Domont, Gilberto B., Velasquez, Erika, Li, Dong, Liu, Siqi, Wang, Quanhui, He, Qing-Yu, Menon, Rajasree, Guan, Yuanfang, Corrales, Fernando J., Segura, Victor, Casal, J. Ignacio, Pascual-Montano, Alberto, Albar, Juan P., Fuentes, Manuel, Gonzalez-Gonzalez, Maria, Diez, Paula, Ibarrola, Nieves, Degano, Rosa M., Mohammed, Yassene, Borchers, Christoph H., Urbani, Andrea, Soggiu, Alessio, Yamamoto, Tadashi, Salekdeh, Ghasem Hosseini, Archakov, Alexander, Ponomarenko, Elena, Lisitsa, Andrey, Lichti, Cheryl F., Mostovenko, Ekaterina, Kroes, Roger A., Rezeli, Melinda, Vegvari, Akos, Fehniger, Thomas E., Bischoff, Rainer, Vizcaino, Juan Antonio, Deutsch, Eric W., Lane, Lydie, Nilsson, Carol L., Marko-Varga, Gyorgy, Omenn, Gilbert S., Jeong, Seul-Ki, Lim, Jong-Sun, Paik, Young-Ki, and Hancock, William S. more...

Abstract

This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological samples that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP's activities; therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper's content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wild (http://c-hpp.webhosting.rug.nl/) and in the Supporting Information., QC 20151022 more...

Published
2015
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6. Quest for Missing Proteins: Update 2015 on Chromosome-Centric Human Proteome Project

Author

Horvatovich, Peter, Lundberg, Emma K., Chen, Yu Ju, Sung, Ting Yi, He, Fuchu, Nice, Ec, Goode, Robert J, Yu, Simon, Ranganathan, Shoba, Baker, Mark S, Domont, Gb, Velasquez, Erika, Li, Dong, Liu, Siqi, Wang, Quanhui, He, Qing Yu, Menon, Rajasree, Guan, Yuanfang, Corrales, Fj, Segura, Victor, Casal, Ji, Pascual Montano, A, Albar, Jp, Fuentes, Manuel, Gonzalez Gonzalez, M, Diez, Paula, Ibarrola, Nieve, Degano, Rosa M, Mohammed, Yassene And Borcher, Urbani, Andrea, Soggiu, Alessio, Yamamoto, Tadashi, Salekdeh, Ghasem Hosseini, Archakov, Alexander, Ponomarenko, Elena, Lisitsa, Andrey, Lichti, Cheryl F, Mostovenko, Ekaterina, Kroes, Roger A, Rezeli, Melinda, Vegvari, Ako, Fehniger, Thomas E, Bischoff, Rainer, Vizcaino, Juan Antonio, Deutsch, Eric W, Lane, Lydie, Nilsson, Carol L, Marko Varga, Gyorgy, Omenn, Gilbert S, Jeong, Seul Ki, Lim, Jong Sun, Paik, Young Ki, Hancock, William S., Urbani, Andrea (ORCID:0000-0001-9168-3174), Horvatovich, Peter, Lundberg, Emma K., Chen, Yu Ju, Sung, Ting Yi, He, Fuchu, Nice, Ec, Goode, Robert J, Yu, Simon, Ranganathan, Shoba, Baker, Mark S, Domont, Gb, Velasquez, Erika, Li, Dong, Liu, Siqi, Wang, Quanhui, He, Qing Yu, Menon, Rajasree, Guan, Yuanfang, Corrales, Fj, Segura, Victor, Casal, Ji, Pascual Montano, A, Albar, Jp, Fuentes, Manuel, Gonzalez Gonzalez, M, Diez, Paula, Ibarrola, Nieve, Degano, Rosa M, Mohammed, Yassene And Borcher, Urbani, Andrea, Soggiu, Alessio, Yamamoto, Tadashi, Salekdeh, Ghasem Hosseini, Archakov, Alexander, Ponomarenko, Elena, Lisitsa, Andrey, Lichti, Cheryl F, Mostovenko, Ekaterina, Kroes, Roger A, Rezeli, Melinda, Vegvari, Ako, Fehniger, Thomas E, Bischoff, Rainer, Vizcaino, Juan Antonio, Deutsch, Eric W, Lane, Lydie, Nilsson, Carol L, Marko Varga, Gyorgy, Omenn, Gilbert S, Jeong, Seul Ki, Lim, Jong Sun, Paik, Young Ki, Hancock, William S., and Urbani, Andrea (ORCID:0000-0001-9168-3174) more...

Abstract

This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological samples that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP's activities; therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper's content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wild (http://c-hpp.webhosting.rug.nl/) and in the Supporting Information. more...

Published
2015

7. A Chromosome-centric Human Proteome Project (C-HPP) to Characterize the Sets of Proteins Encoded in Chromosome 17

Author

Liu, Suli, Im, Hogune, Bairoch, Amos, Cristofanilli, Massimo, Chen, Rui, Deutsch, Eric W., Dalton, Stephen, Fenyo, David, Fanayan, Susan, Gates, Chris, Gaudet, Pascale, Hincapie, Marina, Hanash, Samir, Kim, Hoguen, Jeong, Seul-Ki, Lundberg, Emma, Mias, George, Menon, Rajasree, Mu, Zhaomei, Nice, Edouard, Paik, Young-Ki, Uhlén, Mathias, Wells, Lance, Wu, Shiaw-Lin, Yan, Fangfei, Zhang, Fan, Zhang, Yue, Snyder, Michael, Omenn, Gilbert S., Beavis, Ronald C., Hancock, William S., Liu, Suli, Im, Hogune, Bairoch, Amos, Cristofanilli, Massimo, Chen, Rui, Deutsch, Eric W., Dalton, Stephen, Fenyo, David, Fanayan, Susan, Gates, Chris, Gaudet, Pascale, Hincapie, Marina, Hanash, Samir, Kim, Hoguen, Jeong, Seul-Ki, Lundberg, Emma, Mias, George, Menon, Rajasree, Mu, Zhaomei, Nice, Edouard, Paik, Young-Ki, Uhlén, Mathias, Wells, Lance, Wu, Shiaw-Lin, Yan, Fangfei, Zhang, Fan, Zhang, Yue, Snyder, Michael, Omenn, Gilbert S., Beavis, Ronald C., and Hancock, William S. more...

Abstract

We report progress assembling the parts list for chromosome 17 and illustrate the various processes that we have developed to integrate available data from diverse genomic and proteomic knowledge bases. As primary resources, we have used GPMDB, neXtProt, PeptideAtlas, Human Protein Atlas (HPA), and GeneCards. All sites share the common resource of Ensembl for the genome modeling information. We have defined the chromosome 17 parts list with the following information: 1169 protein-coding genes, the numbers of proteins confidently identified by various experimental approaches as documented in GPMDB, neXtProt, PeptideAtlas, and HPA, examples of typical data sets obtained by RNASeq and proteomic studies of epithelial derived tumor cell lines (disease proteome) and a normal proteome (peripheral mononuclear cells), reported evidence of post-translational modifications, and examples of alternative splice variants (ASVs). We have constructed a list of the 59 "missing" proteins as well as 201 proteins that have inconclusive mass spectrometric (MS) identifications. In this report we have defined a process to establish a baseline for the incorporation of new evidence on protein identification and characterization as well as related information from transcriptome analyses. This initial list of "missing" proteins that will guide the selection of appropriate samples for discovery studies as well as antibody reagents. Also we have illustrated the significant diversity of protein variants (including post-translational modifications, PTMs) using regions on chromosome 17 that contain important oncogenes. We emphasize the need for mandated deposition of proteomics data in public databases, the further development of improved PTM, ASV, and single nucleotide variant (SNV) databases, and the construction of Web sites that can integrate and regularly update such information. In addition, we describe the distribution of both clustered and scattered sets of protein families on the chromosom, QC 20130306 more...

Published
2013
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8. A mouse plasma peptide atlas as a resource for disease proteomics

Author

Koch Institute for Integrative Cancer Research at MIT, Jacks, Tyler E., Zhang, Qing, Menon, Rajasree, Wang, Hong, Bardeesy, Nabeel, Dinulescu, Daniela M., Kucherlapati, Raju, Politi, Katerina, Aebersold, Ruedi, Deutsch, Eric W., Pitteri, Sharon J., Faca, Vitor M., Newcomb, Lisa F., DePinho, Ronald A., Hung, Kenneth E., Omenn, Gilbert S., States, David J., Hanash, Samir M., Jacks, Tyler E, Koch Institute for Integrative Cancer Research at MIT, Jacks, Tyler E., Zhang, Qing, Menon, Rajasree, Wang, Hong, Bardeesy, Nabeel, Dinulescu, Daniela M., Kucherlapati, Raju, Politi, Katerina, Aebersold, Ruedi, Deutsch, Eric W., Pitteri, Sharon J., Faca, Vitor M., Newcomb, Lisa F., DePinho, Ronald A., Hung, Kenneth E., Omenn, Gilbert S., States, David J., Hanash, Samir M., and Jacks, Tyler E more...

Abstract

We present an in-depth analysis of mouse plasma leading to the development of a publicly available repository composed of 568 liquid chromatography-tandem mass spectrometry runs. A total of 13,779 distinct peptides have been identified with high confidence. The corresponding approximately 3,000 proteins are estimated to span a 7 logarithmic range of abundance in plasma. A major finding from this study is the identification of novel isoforms and transcript variants not previously predicted from genome analysis., National Heart, Lung, and Blood Institute (contract no. N01-HV-28179), National Cancer Institute (U.S.) more...

Published
2010

9. Systematic comparison of the human saliva and plasma proteomes

Author

Departments of Medicine and Genetics and Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, MI, USA, Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, USA, EMBL Outstation, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK, Calibrant Biosystems, Gaithersburg, MD, USA, Biomarkers and Systems Biology Center, Research Triangle Institute, Research Triangle, NC, USA, UCLA School of Dentistry and UCLA Dental Research Institute, University of California-Los Angeles, Los Angeles, CA, USA, Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA, Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA, College of Dentistry, New York University, New York, NY, USA, Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, CA, USA, Department of Oral Medicine, Diagnosis, and Radiology, School of Dentistry, University of Minnesota, Minneapolis, MN, USA, Scripps Research Institute, La Jolla, CA, USA, Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, USA ; Department of Biological Chemistry, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA ; Additional corresponding author, UCLA School of Dentistry and UCLA Dental Research Institute, University of California-Los Angeles, Los Angeles, CA, USA ; University of California-Los Angeles, School of Dentistry, 73-017 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA Fax: +1-310-825-7609, Yan, Weihong, Apweiler, Rolf, Balgley, Brian M., Boontheung, Pinmanee, Bundy, Jonathan L., Cargile, Benjamin J., Cole, Steve, Fang, Xueping, Gonzalez-Begne, Mireya, Griffin, Timothy J., Hagen, Fred, Hu, Shen, Wolinsky, Lawrence E., Lee, Cheng S., Malamud, Daniel, Melvin, James E., Menon, Rajasree, Mueller, Michael, Qiao, Renli, Rhodus, Nelson L., Sevinsky, Joel R., States, David, Stephenson, James L., Than, Shawn, Yates, John R., Yu, Weixia, Xie, Hongwei, Xie, Yongming, Omenn, Gilbert S., Loo, Joseph A., Wong, David T., Departments of Medicine and Genetics and Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, MI, USA, Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, USA, EMBL Outstation, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK, Calibrant Biosystems, Gaithersburg, MD, USA, Biomarkers and Systems Biology Center, Research Triangle Institute, Research Triangle, NC, USA, UCLA School of Dentistry and UCLA Dental Research Institute, University of California-Los Angeles, Los Angeles, CA, USA, Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA, Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA, College of Dentistry, New York University, New York, NY, USA, Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, CA, USA, Department of Oral Medicine, Diagnosis, and Radiology, School of Dentistry, University of Minnesota, Minneapolis, MN, USA, Scripps Research Institute, La Jolla, CA, USA, Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, USA ; Department of Biological Chemistry, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA ; Additional corresponding author, UCLA School of Dentistry and UCLA Dental Research Institute, University of California-Los Angeles, Los Angeles, CA, USA ; University of California-Los Angeles, School of Dentistry, 73-017 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA Fax: +1-310-825-7609, Yan, Weihong, Apweiler, Rolf, Balgley, Brian M., Boontheung, Pinmanee, Bundy, Jonathan L., Cargile, Benjamin J., Cole, Steve, Fang, Xueping, Gonzalez-Begne, Mireya, Griffin, Timothy J., Hagen, Fred, Hu, Shen, Wolinsky, Lawrence E., Lee, Cheng S., Malamud, Daniel, Melvin, James E., Menon, Rajasree, Mueller, Michael, Qiao, Renli, Rhodus, Nelson L., Sevinsky, Joel R., States, David, Stephenson, James L., Than, Shawn, Yates, John R., Yu, Weixia, Xie, Hongwei, Xie, Yongming, Omenn, Gilbert S., Loo, Joseph A., and Wong, David T. more...

Abstract

The proteome of human salivary fluid has the potential to open new doors for disease biomarker discovery. A recent study to comprehensively identify and catalog the human ductal salivary proteome led to the compilation of 1166 proteins. The protein complexity of both saliva and plasma is large, suggesting that a comparison of these two proteomes will provide valuable insight into their physiological significance and an understanding of the unique and overlapping disease diagnostic potential that each fluid provides. To create a more comprehensive catalog of human salivary proteins, we have first compiled an extensive list of proteins from whole saliva (WS) identified through MS experiments. The WS list is thereafter combined with the proteins identified from the ductal parotid, and submandibular and sublingual (parotid/SMSL) salivas. In parallel, a core dataset of the human plasma proteome with 3020 protein identifications was recently released. A total of 1939 nonredundant salivary proteins were compiled from a total of 19 14474 unique peptide sequences identified from whole and ductal salivas[semi] 740 out of the total 1939 salivary proteins were identified in both whole and ductal saliva. A total of 597 of the salivary proteins have been observed in plasma. Gene ontology (GO) analysis showed similarities in the distributions of the saliva and plasma proteomes with regard to cellular localization, biological processes, and molecular function, but revealed differences which may be related to the different physiological functions of saliva and plasma. The comprehensive catalog of the salivary proteome and its comparison to the plasma proteome provides insights useful for future study, such as exploration of potential biomarkers for disease diagnostics. more...

Published
2009

10. Human Proteinpedia enables sharing of human protein data

Author

Mathivanan, Suresh, Ahmed, Mukhtar, Ahn, Natalie G, Alexandre, Hainard, Amanchy, Ramars, Andrews, Philip C, Bader, Joel S, Balgley, Brian M, Bantscheff, Marcus, Bennett, Keiryn L, Björling, Erik, Blagoev, Blagoy, Bose, Ron, Brahmachari, Samir K, Burlingame, Alma S, Bustelo, Xosé R, Cagney, Gerard, Cantin, Greg T, Cardasis, Helene L, Celis, Julio E, Chaerkady, Raghothama, Chu, Feixia, Cole, Philip A, Costello, Catherine E, Cotter, Robert J, Crockett, David, DeLany, James P, De Marzo, Angelo M, DeSouza, Leroi V, Deutsch, Eric W, Dransfield, Eric, Drewes, Gerard, Droit, Arnaud, Dunn, Michael J, Elenitoba-Johnson, Kojo, Ewing, Rob M, Eyk, Jennifer Van, Faca, Vitor, Falkner, Jayson, Fang, Xiangming, Fenselau, Catherine, Figeys, Daniel, Gagné, Pierre, Gelfi, Cecilia, Gevaert, Kris, Gimble, Jeffrey M, Gnad, Florian, Goel, Renu, Gromov, Pavel, Hanash, Samir M, Hancock, William S, Harsha, HC, Hart, Gerald, Hays, Faith, He, Fuchu, Hebbar, Prashantha, Helsens, Kenny, Hermeking, Heiko, Hide, Winston, Hjernø, Karin, Hochstrasser, Denis F, Hofmann, Oliver, Horn, David M, Hruban, Ralph H, Ibarrola, Nieves, James, Peter, Jensen, Ole N, Jensen, Pia Hønnerup, Jung, Peter, Kandasamy, Kumaran, Kheterpal, Indu, Kikuno, Reiko F, Korf, Ulrike, Körner, Roman, Kuster, Bernhard, Kwon, Min-Seok, Lee, Hyoung-Joo, Lee, Young-Jin, Lefevre, Michael, Lehvaslaiho, Minna, Lescuyer, Pierre, Levander, Fredrik, Lim, Megan S, Löbke, Christian, Loo, Joseph A, Mann, Matthias, Martens, Lennart, Martinez-Heredia, Juan, McComb, Mark, McRedmond, James, Mehrle, Alexander, Menon, Rajasree, Miller, Christine A, Mischak, Harald, Mohan, S Sujatha, Mohmood, Riaz, Molina, Henrik, Moran, Michael F, Morgan, James D, Moritz, Robert, Morzel, Martine, Muddiman, David C, Nalli, Anuradha, Navarro, J Daniel, Neubert, Thomas A, Ohara, Osamu, Oliva, Rafael, Omenn, Gilbert S, Oyama, Masaaki, Paik, Young-Ki, Pennington, Kyla, Pepperkok, Rainer, Periaswamy, Balamurugan, Petricoin, Emanuel F, Poirier, Guy G, Prasad, T S Keshava, Purvine, Samuel O, Rahiman, B Abdul, Ramachandran, Prasanna, Ramachandra, Y L, Rice, Robert H, Rick, Jens, Ronnholm, Ragna H, Salonen, Johanna, Sanchez, Jean-Charles, Sayd, Thierry, Seshi, Beerelli, Shankari, Kripa, Sheng, Shi Jun, Shetty, Vivekananda, Shivakumar, K, Simpson, Richard J, Sirdeshmukh, Ravi, Michael Siu, K W, Smith, Jeffrey C, Smith, Richard D, States, David J, Sugano, Sumio, Sullivan, Matthew, Superti-Furga, Giulio, Takatalo, Maarit, Thongboonkerd, Visith, Trinidad, Jonathan C, Uhlen, Mathias, Vandekerckhove, Joël, Vasilescu, Julian, Veenstra, Timothy D, Vidal-Taboada, José-Manuel, Vihinen, Mauno, Wait, Robin, Wang, Xiaoyue, Wiemann, Stefan, Wu, Billy, Xu, Tao, Yates, John R, Zhong, Jun, Zhou, Ming, Zhu, Yunping, Zurbig, Petra, Pandey, Akhilesh, Mathivanan, Suresh, Ahmed, Mukhtar, Ahn, Natalie G, Alexandre, Hainard, Amanchy, Ramars, Andrews, Philip C, Bader, Joel S, Balgley, Brian M, Bantscheff, Marcus, Bennett, Keiryn L, Björling, Erik, Blagoev, Blagoy, Bose, Ron, Brahmachari, Samir K, Burlingame, Alma S, Bustelo, Xosé R, Cagney, Gerard, Cantin, Greg T, Cardasis, Helene L, Celis, Julio E, Chaerkady, Raghothama, Chu, Feixia, Cole, Philip A, Costello, Catherine E, Cotter, Robert J, Crockett, David, DeLany, James P, De Marzo, Angelo M, DeSouza, Leroi V, Deutsch, Eric W, Dransfield, Eric, Drewes, Gerard, Droit, Arnaud, Dunn, Michael J, Elenitoba-Johnson, Kojo, Ewing, Rob M, Eyk, Jennifer Van, Faca, Vitor, Falkner, Jayson, Fang, Xiangming, Fenselau, Catherine, Figeys, Daniel, Gagné, Pierre, Gelfi, Cecilia, Gevaert, Kris, Gimble, Jeffrey M, Gnad, Florian, Goel, Renu, Gromov, Pavel, Hanash, Samir M, Hancock, William S, Harsha, HC, Hart, Gerald, Hays, Faith, He, Fuchu, Hebbar, Prashantha, Helsens, Kenny, Hermeking, Heiko, Hide, Winston, Hjernø, Karin, Hochstrasser, Denis F, Hofmann, Oliver, Horn, David M, Hruban, Ralph H, Ibarrola, Nieves, James, Peter, Jensen, Ole N, Jensen, Pia Hønnerup, Jung, Peter, Kandasamy, Kumaran, Kheterpal, Indu, Kikuno, Reiko F, Korf, Ulrike, Körner, Roman, Kuster, Bernhard, Kwon, Min-Seok, Lee, Hyoung-Joo, Lee, Young-Jin, Lefevre, Michael, Lehvaslaiho, Minna, Lescuyer, Pierre, Levander, Fredrik, Lim, Megan S, Löbke, Christian, Loo, Joseph A, Mann, Matthias, Martens, Lennart, Martinez-Heredia, Juan, McComb, Mark, McRedmond, James, Mehrle, Alexander, Menon, Rajasree, Miller, Christine A, Mischak, Harald, Mohan, S Sujatha, Mohmood, Riaz, Molina, Henrik, Moran, Michael F, Morgan, James D, Moritz, Robert, Morzel, Martine, Muddiman, David C, Nalli, Anuradha, Navarro, J Daniel, Neubert, Thomas A, Ohara, Osamu, Oliva, Rafael, Omenn, Gilbert S, Oyama, Masaaki, Paik, Young-Ki, Pennington, Kyla, Pepperkok, Rainer, Periaswamy, Balamurugan, Petricoin, Emanuel F, Poirier, Guy G, Prasad, T S Keshava, Purvine, Samuel O, Rahiman, B Abdul, Ramachandran, Prasanna, Ramachandra, Y L, Rice, Robert H, Rick, Jens, Ronnholm, Ragna H, Salonen, Johanna, Sanchez, Jean-Charles, Sayd, Thierry, Seshi, Beerelli, Shankari, Kripa, Sheng, Shi Jun, Shetty, Vivekananda, Shivakumar, K, Simpson, Richard J, Sirdeshmukh, Ravi, Michael Siu, K W, Smith, Jeffrey C, Smith, Richard D, States, David J, Sugano, Sumio, Sullivan, Matthew, Superti-Furga, Giulio, Takatalo, Maarit, Thongboonkerd, Visith, Trinidad, Jonathan C, Uhlen, Mathias, Vandekerckhove, Joël, Vasilescu, Julian, Veenstra, Timothy D, Vidal-Taboada, José-Manuel, Vihinen, Mauno, Wait, Robin, Wang, Xiaoyue, Wiemann, Stefan, Wu, Billy, Xu, Tao, Yates, John R, Zhong, Jun, Zhou, Ming, Zhu, Yunping, Zurbig, Petra, and Pandey, Akhilesh more...

Abstract

Proteomic technologies, such as yeast two-hybrid, mass spectrometry (MS), protein/peptide arrays and fluorescence microscopy, yield multi-dimensional data sets, which are often quite large and either not published or published as supplementary information that is not easily searchable. Without a system in place for standardizing and sharing data, it is not fruitful for the biomedical community to contribute these types of data to centralized repositories. more...