56 Works

Environmental robustness of the global yeast genetic interaction network

Michael Costanzo, Jing Hou, Vincent Messier, Justin Nelson, Mahfuzur Rahman, Benjamin VanderSluis, Wen Wang, Carles Pons, Catherine Ross, Matej Ušaj, Bryan-Joseph San Luis, Emira Shuteriqi, Elizabeth N. Koch, Patrick Aloy, Chad L. Myers, Charles Boone & Brenda Andrews
Phenotypes associated with genetic variants can be altered by interactions with other genetic variants (GxG), with the environment (GxE), or both (GxGxE). Yeast genetic interactions have been mapped on a global scale, but the environmental influence on the plasticity of genetic networks has not been examined systematically. To assess environmental rewiring of genetic networks, we examined 14 diverse conditions and scored 30,000 functionally representative yeast gene pairs for dynamic, differential interactions. Different conditions revealed novel...

Additional file 1 of Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata

Marina Marcet-Houben, María Alvarado, Ewa Ksiezopolska, Ester Saus, Piet W. J. de Groot & Toni Gabaldón
Additional file 1: Fig S1. Comparison of reference assemblies. Fig S2. Circos plots representing structural variation among strains. Fig S3. Dotplot representing improvements in assembly of strain CAS08-0016. Fig S4. Barplot representing origin of accessory families. Fig S5. Graphical representation of the adhesin detection pipeline. Fig S6. Gains and losses of adhesin families in the C. glabrata strains. Fig S7. Summary of the LongHam pipeline. Fig S8. Example of an adhesin gene cluster. Fig S9....

Additional file 3 of LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

Donatella Delle Cave, Silvia Buonaiuto, Bruno Sainz, Marco Fantuz, Maria Mangini, Alessandro Carrer, Annalisa Di Domenico, Tea Teresa Iavazzo, Gennaro Andolfi, Carme Cortina, Marta Sevillano, Christopher Heeschen, Vincenza Colonna, Marco Corona, Antonio Cucciardi, Martina Di Guida, Eduard Batlle, Annachiara De Luca & Enza Lonardo
Additional file 3: Figure S3. LAMC2 expression correlates with CSC content and function. (a) qPCR analysis of LAMC2 gene expression in adherent cells versus spheres. Data are normalized to GAPDH and are presented as fold change in gene expression relative to adherent cells (indicated as Adh). (b) Western blot analysis of LAMC2 in adherent cells versus spheres. Parallel β-ACTIN immunoblotting was performed. (c) qPCR analysis for CD44, CD133 and L1CAM genes in adherent cells versus...

Additional file 9 of LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

Donatella Delle Cave, Silvia Buonaiuto, Bruno Sainz, Marco Fantuz, Maria Mangini, Alessandro Carrer, Annalisa Di Domenico, Tea Teresa Iavazzo, Gennaro Andolfi, Carme Cortina, Marta Sevillano, Christopher Heeschen, Vincenza Colonna, Marco Corona, Antonio Cucciardi, Martina Di Guida, Eduard Batlle, Annachiara De Luca & Enza Lonardo
Additional file 9: Figure S9. Global gene expression profiles of LAMC2-EGFP+ and EGFP--derived tumors. Heat map of differentially expressed genes in EGFP+ and EGFP- cells isolated from tumors.

Integrative pathway enrichment analysis of multivariate omics data

Marta Paczkowska, Jonathan Barenboim, Nardnisa Sintupisut, Natalie S Fox, Helen Zhu, Diala Abd-Rabbo, Miles W Mee, Paul C Boutros, Federico Abascal, Samirkumar B Amin, Gary D Bader, Rameen Beroukhim, Johanna Bertl, Keith A Boroevich, Søren Brunak, Peter J Campbell, Joana Carlevaro-Fita, Dimple Chakravarty, Calvin Wing Yiu Chan, Ken Chen, Jung Kyoon Choi, Jordi Deu-Pons, Priyanka Dhingra, Klev Diamanti, Lars Feuerbach … & L van’t Veer
Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated...

UntimBIO-Llauger-et-al-2023-movieS3

Gabriela Llauger, Roberto Melero, demian monti, Gabriela Sycz, Cristián Huck-Iriart, María Laura Cerutti, Sebastián Klinke, Evelyn Mikkelsen, Ariel Tijman, Rocío Arranz, Victoria Alfonso, Sofía M. Arellano, Fernando Alberto Goldbaum, Yann G. J. Sterckx, Jose Maria Carazo, Sergio B. Kaufman, Pablo D. Dans, Mariana del Vas & Lisandro H. Otero
Movie S3. Animation of the reconstructed model of the P9-1 dodecamer and its MD simulation. The model is colored according to its secondary structure elements as in Fig. 3A. At the beginning of the movie, only one dimer is shown, and the other five appear sequentially to illustrate the dodecamer construction. Then, the MD animation starts, and residues that were fixed in space as found experimentally are colored in light gray using Connolly surface....

Additional file 7 of LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

Donatella Delle Cave, Silvia Buonaiuto, Bruno Sainz, Marco Fantuz, Maria Mangini, Alessandro Carrer, Annalisa Di Domenico, Tea Teresa Iavazzo, Gennaro Andolfi, Carme Cortina, Marta Sevillano, Christopher Heeschen, Vincenza Colonna, Marco Corona, Antonio Cucciardi, Martina Di Guida, Eduard Batlle, Annachiara De Luca & Enza Lonardo
Additional file 7: Figure S7. Generation of LAMC2-EGFP knock-in human PDAC cells. (a) Flow cytometry for IRFP in PDAC cells 48 hours post-nucleofection. All cytometry gates were established based on isotype controls. (b) Flow cytometry for EGFP in PDAC cells 20 days post-nucleofection. All cytometry gates were established based on isotype controls. (c) PCR gDNA specific integration analysis. The positions of primers are indicated by arrows. (d) FACS profiles showing the expression of EGFP in...

Additional file 8 of LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

Donatella Delle Cave, Silvia Buonaiuto, Bruno Sainz, Marco Fantuz, Maria Mangini, Alessandro Carrer, Annalisa Di Domenico, Tea Teresa Iavazzo, Gennaro Andolfi, Carme Cortina, Marta Sevillano, Christopher Heeschen, Vincenza Colonna, Marco Corona, Antonio Cucciardi, Martina Di Guida, Eduard Batlle, Annachiara De Luca & Enza Lonardo
Additional file 8: Figure S8. Characterization of human LAMC2-EGFP PDAC cells in vitro and in vivo. (a) Representative images of EGFP+ and EGFP-cells grown in Matrigel. (b) Organoid formation capacity of EGFP+ and EGFP-cells. (c) Quantification of organoid size of EGFP+ and EGFP-cells. (d) qPCR analysis for LAMC2, EMT, MMP2 and MMP10 gene expression in EGFP+ and EGFP-cells. Data are normalized to GAPDH and are presented as fold change in gene expression relative to the...

LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

Donatella Delle Cave, Silvia Buonaiuto, Bruno Sainz, Marco Fantuz, Maria Mangini, Alessandro Carrer, Annalisa Di Domenico, Tea Teresa Iavazzo, Gennaro Andolfi, Carme Cortina, Marta Sevillano, Christopher Heeschen, Vincenza Colonna, Marco Corona, Antonio Cucciardi, Martina Di Guida, Eduard Batlle, Annachiara De Luca & Enza Lonardo
Abstract Background Tumor-initiating cells (TIC), also known as cancer stem cells, are considered a specific subpopulation of cells necessary for cancer initiation and metastasis; however, the mechanisms by which they acquire metastatic traits are not well understood. Methods LAMC2 transcriptional levels were evaluated using publicly available transcriptome data sets, and LAMC2 immunohistochemistry was performed using a tissue microarray composed of PDAC and normal pancreas tissues. Silencing and tracing of LAMC2 was performed using lentiviral shRNA...

Divergent mutational processes distinguish hypoxic and normoxic tumours

Vinayak Bhandari, Constance H Li, Robert G Bristow, Paul C Boutros, Lauri A Aaltonen, Federico Abascal, Adam Abeshouse, Hiroyuki Aburatani, David J Adams, Nishant Agrawal, Keun Soo Ahn, Sung-Min Ahn, Hiroshi Aikata, Rehan Akbani, Kadir C Akdemir, Hikmat Al-Ahmadie, Sultan T Al-Sedairy, Fatima Al-Shahrour, Malik Alawi, Monique Albert, Kenneth Aldape, Ludmil B Alexandrov, Adrian Ally, Kathryn Alsop, Eva G Alvarez … & Christian von Mering
Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning...

UntimBIO-Llauger-et-al-2023-movieS3

Gabriela Llauger, Roberto Melero, demian monti, Gabriela Sycz, Cristián Huck-Iriart, María Laura Cerutti, Sebastián Klinke, Evelyn Mikkelsen, Ariel Tijman, Rocío Arranz, Victoria Alfonso, Sofía M. Arellano, Fernando Alberto Goldbaum, Yann G. J. Sterckx, Jose Maria Carazo, Sergio B. Kaufman, Pablo D. Dans, Mariana del Vas & Lisandro H. Otero
Movie S3. Animation of the reconstructed model of the P9-1 dodecamer and its MD simulation. The model is colored according to its secondary structure elements as in Fig. 3A. At the beginning of the movie, only one dimer is shown, and the other five appear sequentially to illustrate the dodecamer construction. Then, the MD animation starts, and residues that were fixed in space as found experimentally are colored in light gray using Connolly surface....

A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Wei Jiao, Gurnit Atwal, Paz Polak, Rosa Karlic, Edwin Cuppen, Fatima Al-Shahrour, Peter J Bailey, Andrew V Biankin, Paul C Boutros, Peter J Campbell, David K Chang, Susanna L Cooke, Vikram Deshpande, Bishoy M Faltas, William C Faquin, Levi Garraway, Gad Getz, Sean M Grimmond, Syed Haider, Katherine A Hoadley, Vera B Kaiser, Mamoru Kato, Kirsten Kübler, Alexander J Lazar, Constance H Li … & Christian von Mering
In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24...

A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Wei Jiao, Gurnit Atwal, Paz Polak, Rosa Karlic, Edwin Cuppen, Fatima Al-Shahrour, Peter J Bailey, Andrew V Biankin, Paul C Boutros, Peter J Campbell, David K Chang, Susanna L Cooke, Vikram Deshpande, Bishoy M Faltas, William C Faquin, Levi Garraway, Gad Getz, Sean M Grimmond, Syed Haider, Katherine A Hoadley, Vera B Kaiser, Mamoru Kato, Kirsten Kübler, Alexander J Lazar, Constance H Li … & Christian von Mering
In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24...

Combined burden and functional impact tests for cancer driver discovery using DriverPower

Shimin Shuai, Federico Abascal, Samirkumar B Amin, Gary D Bader, Pratiti Bandopadhayay, Jonathan Barenboim, Rameen Beroukhim, Johanna Bertl, Keith A Boroevich, Søren Brunak, Peter J Campbell, Joana Carlevaro-Fita, Dimple Chakravarty, Calvin Wing Yiu Chan, Ken Chen, Jung Kyoon Choi, Jordi Deu-Pons, Priyanka Dhingra, Klev Diamanti, Lars Feuerbach, J Lynn Fink, Nuno A Fonseca, Joan Frigola, Carlo Gambacorti-Passerini, Dale W Garsed … & L van’t Veer
The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features...

Additional file 3 of Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata

Marina Marcet-Houben, María Alvarado, Ewa Ksiezopolska, Ester Saus, Piet W. J. de Groot & Toni Gabaldón
Additional file 3. Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata.

Additional file 3 of Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata

Marina Marcet-Houben, María Alvarado, Ewa Ksiezopolska, Ester Saus, Piet W. J. de Groot & Toni Gabaldón
Additional file 3. Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata.

Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata

Marina Marcet-Houben, María Alvarado, Ewa Ksiezopolska, Ester Saus, Piet W. J. de Groot & Toni Gabaldón
Abstract Background Candida glabrata is an opportunistic yeast pathogen thought to have a large genetic and phenotypic diversity and a highly plastic genome. However, the lack of chromosome-level genome assemblies representing this diversity limits our ability to accurately establish how chromosomal structure and gene content vary across strains. Results Here, we expanded publicly available assemblies by using long-read sequencing technologies in twelve diverse strains, obtaining a final set of twenty-one chromosome-level genomes spanning the known...

Additional file 10 of LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

Donatella Delle Cave, Silvia Buonaiuto, Bruno Sainz, Marco Fantuz, Maria Mangini, Alessandro Carrer, Annalisa Di Domenico, Tea Teresa Iavazzo, Gennaro Andolfi, Carme Cortina, Marta Sevillano, Christopher Heeschen, Vincenza Colonna, Marco Corona, Antonio Cucciardi, Martina Di Guida, Eduard Batlle, Annachiara De Luca & Enza Lonardo
Additional file 10: Figure S10. Inhibition of transforming growth factor beta (TGF-β) signaling blocks LAMC2-induced metastasis. (a) Enrichment plots for pancreatic cancer, focal adhesion, hypoxia, MAPK signaling, glycolysis and gluconeogenesis pathways in EGFP+ versus EGFP- cells isolated by FACS from subcutaneous tumors. (b) Western blot analysis for pSMAD2 and SMAD2 in EGFP- versus EGFP+ PANC-1 and #253 cells. Parallel GAPDH immunoblotting was performed. (c) Flow cytometry quantification of EGFP and ALK5-TGFβR1 in EGFP- and EGFP+...

Additional file 4 of LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

Donatella Delle Cave, Silvia Buonaiuto, Bruno Sainz, Marco Fantuz, Maria Mangini, Alessandro Carrer, Annalisa Di Domenico, Tea Teresa Iavazzo, Gennaro Andolfi, Carme Cortina, Marta Sevillano, Christopher Heeschen, Vincenza Colonna, Marco Corona, Antonio Cucciardi, Martina Di Guida, Eduard Batlle, Annachiara De Luca & Enza Lonardo
Additional file 4: Figure S4. Knockdown of LAMC2 does not affect cell growth. (a) Western blot analysis of LAMC2 in sh empty and LAMC2 knockdown cells. Parallel β-ACTIN immunoblotting was performed. (b) qPCR analysis for LAMC2 and CD44 gene expression in sh empty and LAMC2 knockdown cells. Data are normalized to GAPDH and are presented as fold change in gene expression relative to sh empty. (c) Representative images of sh empty and LAMC2 knockdown cells...

Additional file 6 of LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

Donatella Delle Cave, Silvia Buonaiuto, Bruno Sainz, Marco Fantuz, Maria Mangini, Alessandro Carrer, Annalisa Di Domenico, Tea Teresa Iavazzo, Gennaro Andolfi, Carme Cortina, Marta Sevillano, Christopher Heeschen, Vincenza Colonna, Marco Corona, Antonio Cucciardi, Martina Di Guida, Eduard Batlle, Annachiara De Luca & Enza Lonardo
Additional file 6: Figure S6. Knockdown of LAMC2 affects tumorigenicity. (a) Representative images from a gelatin degradation assay of sh empty and LAMC2 knockdown cells. Nuclei were stained with Hoechst 33342 (blue), green represents actin (Alexa Fluor™ 488 Phalloidin) and red illustrates gelatin (Rodhamine). The white dashed line circles indicate the areas of degradation. (b) Degradation potential of sh empty and LAMC2 knockdown cells. (c) qPCR analysis for EMT genes in sh empty and LAMC2...

Combined burden and functional impact tests for cancer driver discovery using DriverPower

Shimin Shuai, Federico Abascal, Samirkumar B Amin, Gary D Bader, Pratiti Bandopadhayay, Jonathan Barenboim, Rameen Beroukhim, Johanna Bertl, Keith A Boroevich, Søren Brunak, Peter J Campbell, Joana Carlevaro-Fita, Dimple Chakravarty, Calvin Wing Yiu Chan, Ken Chen, Jung Kyoon Choi, Jordi Deu-Pons, Priyanka Dhingra, Klev Diamanti, Lars Feuerbach, J Lynn Fink, Nuno A Fonseca, Joan Frigola, Carlo Gambacorti-Passerini, Dale W Garsed … & L van’t Veer
The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features...

Integrative pathway enrichment analysis of multivariate omics data

Marta Paczkowska, Jonathan Barenboim, Nardnisa Sintupisut, Natalie S Fox, Helen Zhu, Diala Abd-Rabbo, Miles W Mee, Paul C Boutros, Federico Abascal, Samirkumar B Amin, Gary D Bader, Rameen Beroukhim, Johanna Bertl, Keith A Boroevich, Søren Brunak, Peter J Campbell, Joana Carlevaro-Fita, Dimple Chakravarty, Calvin Wing Yiu Chan, Ken Chen, Jung Kyoon Choi, Jordi Deu-Pons, Priyanka Dhingra, Klev Diamanti, Lars Feuerbach … & L van’t Veer
Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated...

Pathway and network analysis of more than 2500 whole cancer genomes

Matthew A Reyna, David Haan, Marta Paczkowska, Lieven PC Verbeke, Miguel Vazquez, Abdullah Kahraman, Sergio Pulido-Tamayo, Jonathan Barenboim, Lina Wadi, Priyanka Dhingra, Raunak Shrestha, Gad Getz, Michael S Lawrence, Jakob Skou Pedersen, Mark A Rubin, David A Wheeler, Søren Brunak, Jose MG Izarzugaza, Ekta Khurana, Kathleen Marchal, Christian von Mering, S Cenk Sahinalp, Alfonso Valencia, Federico Abascal, Samirkumar B Amin … & L van’t Veer
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding...

Pathway and network analysis of more than 2500 whole cancer genomes

Matthew A Reyna, David Haan, Marta Paczkowska, Lieven PC Verbeke, Miguel Vazquez, Abdullah Kahraman, Sergio Pulido-Tamayo, Jonathan Barenboim, Lina Wadi, Priyanka Dhingra, Raunak Shrestha, Gad Getz, Michael S Lawrence, Jakob Skou Pedersen, Mark A Rubin, David A Wheeler, Søren Brunak, Jose MG Izarzugaza, Ekta Khurana, Kathleen Marchal, Christian von Mering, S Cenk Sahinalp, Alfonso Valencia, Federico Abascal, Samirkumar B Amin … & L van’t Veer
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding...

mBIO-Llauger-et-al-2023-movieS1

Gabriela Llauger, Roberto Melero, demian monti, Gabriela Sycz, Cristián Huck-Iriart, María Laura Cerutti, Sebastián Klinke, Evelyn Mikkelsen, Ariel Tijman, Rocío Arranz, Victoria Alfonso, Sofía M. Arellano, Fernando Alberto Goldbaum, Yann G. J. Sterckx, Jose Maria Carazo, Sergio B. Kaufman, Pablo D. Dans, Mariana del Vas & Lisandro H. Otero
Movie S1. Animation of the reconstructed model of the P9-1 dimer and its MD simulation. The model is colored according to secondary structure elements as in Fig. 3A. When the MD animation starts, residues that were fixed in space as found experimentally are colored in light gray. The MD animation displays the last 3 μs of a 4 μs simulation.

Registration Year

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Affiliations

  • Institute for Research in Biomedicine
    56
  • Institució Catalana de Recerca i Estudis Avançats
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  • University of Padua
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  • Shanghai Jiao Tong University
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  • Washington University in St. Louis
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