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Putative cell type discovery from single-cell gene expression data.

Zhichao Miao, Pablo Moreno, Ni Huang, Irene Papatheodorou, Alvis Brazma, Sarah A Teichmann,

We present the Single-Cell Clustering Assessment Framework, a method for the automated identification of putative cell types from single-cell RNA sequencing (scRNA-seq) data. By iteratively applying a machine learning approach to a given set of cells, we simultaneously identify distinct cell groups and a weighted list of feature genes for ... Read more >>

Nat. Methods (Nature methods)
[2020, 17(6):621-628]

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Dysregulation at multiple points of the kynurenine pathway is a ubiquitous feature of renal cancer: implications for tumour immune evasion.

Nick Hornigold, Karen R Dunn, Rachel A Craven, Alexandre Zougman, Sebastian Trainor, Rebecca Shreeve, Joanne Brown, Helen Sewell, Michael Shires, Margaret Knowles, Tsutomu Fukuwatari, Eamonn R Maher, Julie Burns, Selina Bhattarai, Mini Menon, Alvis Brazma, Ghislaine Scelo, Lara Feulner, Yasser Riazalhosseini, Mark Lathrop, Adrian Harris, Peter J Selby, Rosamonde E Banks, Naveen S Vasudev,

BACKGROUND:Indoleamine 2,3-dioxygenase (IDO), the first step in the kynurenine pathway (KP), is upregulated in some cancers and represents an attractive therapeutic target given its role in tumour immune evasion. However, the recent failure of an IDO inhibitor in a late phase trial raises questions about this strategy. METHODS:Matched renal cell ... Read more >>

Br. J. Cancer (British journal of cancer)
[2020, :]

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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes.

Waradon Sungnak, Ni Huang, Christophe Bécavin, Marijn Berg, Rachel Queen, Monika Litvinukova, Carlos Talavera-López, Henrike Maatz, Daniel Reichart, Fotios Sampaziotis, Kaylee B Worlock, Masahiro Yoshida, Josephine L Barnes, ,

We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial ... Read more >>

Nat. Med. (Nature medicine)
[2020, 26(5):681-687]

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Tumour gene expression signature in primary melanoma predicts long-term outcomes: A prospective multicentre study

Manik Garg, Dominique-Laurent Couturier, Jérémie Nsengimana, Nuno Fonseca, Matthew Wongchenko, Yibing Yan, Martin Lauss, Göran Jönsson, Julia Newton-Bishop, Christine Parkinson, Mark Middleton, Tim Bishop, Pippa Corrie, David Adams, Alvis Brazma, Roy Rabbie,

Abstract Purpose Predicting outcomes after resection of primary melanoma remains crude, primarily based on tumour thickness. We explored gene expression signatures for their ability to better predict outcomes. Methods Differential expression analysis of 194 primary melanomas resected from patients who either developed distant metastasis (n=89) or did not (n=105) was ... Read more >>

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High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.

Yiqun Zhang, Fengju Chen, Nuno A Fonseca, Yao He, Masashi Fujita, Hidewaki Nakagawa, Zemin Zhang, Alvis Brazma, , , Chad J Creighton, ,

The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for ... Read more >>

Nat Commun (Nature communications)
[2020, 11(1):736]

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Genomic basis for RNA alterations in cancer.

, Claudia Calabrese, Natalie R Davidson, Deniz Demircioğlu, Nuno A Fonseca, Yao He, André Kahles, Kjong-Van Lehmann, Fenglin Liu, Yuichi Shiraishi, Cameron M Soulette, Lara Urban, Liliana Greger, Siliang Li, Dongbing Liu, Marc D Perry, Qian Xiang, Fan Zhang, Junjun Zhang, Peter Bailey, Serap Erkek, Katherine A Hoadley, Yong Hou, Matthew R Huska, Helena Kilpinen, Jan O Korbel, Maximillian G Marin, Julia Markowski, Tannistha Nandi, Qiang Pan-Hammarström, Chandra Sekhar Pedamallu, Reiner Siebert, Stefan G Stark, Hong Su, Patrick Tan, Sebastian M Waszak, Christina Yung, Shida Zhu, Philip Awadalla, Chad J Creighton, Matthew Meyerson, B F Francis Ouellette, Kui Wu, Huanming Yang, , Alvis Brazma, Angela N Brooks, Jonathan Göke, Gunnar Rätsch, Roland F Schwarz, Oliver Stegle, Zemin Zhang, ,

Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small ... Read more >>

Nature (Nature)
[2020, 578(7793):129-136]

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Pan-cancer analysis of whole genomes.

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Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) ... Read more >>

Nature (Nature)
[2020, 578(7793):82-93]

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Expression Atlas update: from tissues to single cells.

Irene Papatheodorou, Pablo Moreno, Jonathan Manning, Alfonso Muñoz-Pomer Fuentes, Nancy George, Silvie Fexova, Nuno A Fonseca, Anja Füllgrabe, Matthew Green, Ni Huang, Laura Huerta, Haider Iqbal, Monica Jianu, Suhaib Mohammed, Lingyun Zhao, Andrew F Jarnuczak, Simon Jupp, John Marioni, Kerstin Meyer, Robert Petryszak, Cesar Augusto Prada Medina, Carlos Talavera-López, Sarah Teichmann, Juan Antonio Vizcaino, Alvis Brazma,

Expression Atlas is EMBL-EBI's resource for gene and protein expression. It sources and compiles data on the abundance and localisation of RNA and proteins in various biological systems and contexts and provides open access to this data for the research community. With the increased availability of single cell RNA-Seq datasets ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2020, 48(D1):D77-D83]

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Blood transcriptome profile induced by an efficacious vaccine formulated with salivary antigens from cattle ticks.

Sandra R Maruyama, Benilton Carvalho, Mar González-Porta, Johan Rung, Alvis Brazma, Luiz Gustavo Gardinassi, Beatriz R Ferreira, Tamy M Banin, Cecília J Veríssimo, Luciana M Katiki, Isabel K F de Miranda-Santos,

Ticks cause massive damage to livestock and vaccines are one sustainable alternative for the acaricide poisons currently heavily used to control infestations. An experimental vaccine adjuvanted with alum and composed by four recombinant salivary antigens mined with reverse vaccinology from a transcriptome of salivary glands from Rhipicephalus microplus ticks was ... Read more >>

NPJ Vaccines (NPJ vaccines)
[2019, 4:53]

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A Pan-cancer Transcriptome Analysis Reveals Pervasive Regulation through Alternative Promoters.

Deniz Demircioğlu, Engin Cukuroglu, Martin Kindermans, Tannistha Nandi, Claudia Calabrese, Nuno A Fonseca, André Kahles, Kjong-Van Lehmann, Oliver Stegle, Alvis Brazma, Angela N Brooks, Gunnar Rätsch, Patrick Tan, Jonathan Göke,

Most human protein-coding genes are regulated by multiple, distinct promoters, suggesting that the choice of promoter is as important as its level of transcriptional activity. However, while a global change in transcription is recognized as a defining feature of cancer, the contribution of alternative promoters still remains largely unexplored. Here, ... Read more >>

Cell (Cell)
[2019, 178(6):1465-1477.e17]

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An integrated landscape of protein expression in human cancer

Andrew Jarnuczak, Hanna Najgebauer, Mitra Barzine, Deepti Kundu, Fatemeh Ghavidel, Yasset Perez-Riverol, Irene Papatheodorou, Alvis Brazma, Juan Antonio Vizcaíno,

ABSTRACT Using public proteomics datasets, mostly available through the PRIDE database, we assembled a proteomics resource for 191 cancer cell lines and 246 clinical tumour samples, across 13 cancer lineages. We found that baseline protein abundance in cell lines was generally representative of tumours. However, when considering differences in protein ... Read more >>

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ArrayExpress update - from bulk to single-cell expression data.

Awais Athar, Anja Füllgrabe, Nancy George, Haider Iqbal, Laura Huerta, Ahmed Ali, Catherine Snow, Nuno A Fonseca, Robert Petryszak, Irene Papatheodorou, Ugis Sarkans, Alvis Brazma,

ArrayExpress (https://www.ebi.ac.uk/arrayexpress) is an archive of functional genomics data from a variety of technologies assaying functional modalities of a genome, such as gene expression or promoter occupancy. The number of experiments based on sequencing technologies, in particular RNA-seq experiments, has been increasing over the last few years and submissions of ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2019, 47(D1):D711-D715]

Cited: 6 times

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The PRIDE database and related tools and resources in 2019: improving support for quantification data.

Yasset Perez-Riverol, Attila Csordas, Jingwen Bai, Manuel Bernal-Llinares, Suresh Hewapathirana, Deepti J Kundu, Avinash Inuganti, Johannes Griss, Gerhard Mayer, Martin Eisenacher, Enrique Pérez, Julian Uszkoreit, Julianus Pfeuffer, Timo Sachsenberg, Sule Yilmaz, Shivani Tiwary, Jürgen Cox, Enrique Audain, Mathias Walzer, Andrew F Jarnuczak, Tobias Ternent, Alvis Brazma, Juan Antonio Vizcaíno,

The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world's largest data repository of mass spectrometry-based proteomics data, and is one of the founding members of the global ProteomeXchange (PX) consortium. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2019, 47(D1):D442-D450]

Cited: 224 times

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Publisher Correction: Image Data Resource: a bioimage data integration and publication platform.

Eleanor Williams, Josh Moore, Simon W Li, Gabriella Rustici, Aleksandra Tarkowska, Anatole Chessel, Simone Leo, Bálint Antal, Richard K Ferguson, Ugis Sarkans, Alvis Brazma, Rafael E Carazo Salas, Jason R Swedlow,

This paper was originally published under standard Nature America Inc. copyright. As of the date of this correction, the Resource is available online as an open-access paper with a CC-BY license. No other part of the paper has been changed. ... Read more >>

Nat. Methods (Nature methods)
[2018, 15(11):984]

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An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures.

Grace Collord, Patrick Tarpey, Natalja Kurbatova, Inigo Martincorena, Sebastian Moran, Manuel Castro, Tibor Nagy, Graham Bignell, Francesco Maura, Matthew D Young, Jorge Berna, Jose M C Tubio, Chris E McMurran, Adam M H Young, Mathijs Sanders, Imran Noorani, Stephen J Price, Colin Watts, Elke Leipnitz, Matthias Kirsch, Gabriele Schackert, Danita Pearson, Abel Devadass, Zvi Ram, V Peter Collins, Kieren Allinson, Michael D Jenkinson, Rasheed Zakaria, Khaja Syed, C Oliver Hanemann, Jemma Dunn, Michael W McDermott, Ramez W Kirollos, George S Vassiliou, Manel Esteller, Sam Behjati, Alvis Brazma, Thomas Santarius, Ultan McDermott,

Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):13537]

Cited: 4 times

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Aberration hubs in protein interaction networks highlight actionable targets in cancer.

Mehran Karimzadeh, Pouria Jandaghi, Andreas I Papadakis, Sebastian Trainor, Johan Rung, Mar Gonzàlez-Porta, Ghislaine Scelo, Naveen S Vasudev, Alvis Brazma, Sidong Huang, Rosamonde E Banks, Mark Lathrop, Hamed S Najafabadi, Yasser Riazalhosseini,

Despite efforts for extensive molecular characterization of cancer patients, such as the international cancer genome consortium (ICGC) and the cancer genome atlas (TCGA), the heterogeneous nature of cancer and our limited knowledge of the contextual function of proteins have complicated the identification of targetable genes. Here, we present Aberration Hub ... Read more >>

Oncotarget (Oncotarget)
[2018, 9(38):25166-25180]

Cited: 1 time

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A General Framework for Interrogation of mRNA Stability Programs Identifies RNA-Binding Proteins that Govern Cancer Transcriptomes.

Gabrielle Perron, Pouria Jandaghi, Shraddha Solanki, Maryam Safisamghabadi, Cristina Storoz, Mehran Karimzadeh, Andreas I Papadakis, Madeleine Arseneault, Ghislaine Scelo, Rosamonde E Banks, Jorg Tost, Mark Lathrop, Simon Tanguay, Alvis Brazma, Sidong Huang, Fadi Brimo, Hamed S Najafabadi, Yasser Riazalhosseini,

Widespread remodeling of the transcriptome is a signature of cancer; however, little is known about the post-transcriptional regulatory factors, including RNA-binding proteins (RBPs) that regulate mRNA stability, and the extent to which RBPs contribute to cancer-associated pathways. Here, by modeling the global change in gene expression based on the effect ... Read more >>

Cell Rep (Cell reports)
[2018, 23(6):1639-1650]

Cited: 2 times

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Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes.

David Thybert, Maša Roller, Fábio C P Navarro, Ian Fiddes, Ian Streeter, Christine Feig, David Martin-Galvez, Mikhail Kolmogorov, Václav Janoušek, Wasiu Akanni, Bronwen Aken, Sarah Aldridge, Varshith Chakrapani, William Chow, Laura Clarke, Carla Cummins, Anthony Doran, Matthew Dunn, Leo Goodstadt, Kerstin Howe, Matthew Howell, Ambre-Aurore Josselin, Robert C Karn, Christina M Laukaitis, Lilue Jingtao, Fergal Martin, Matthieu Muffato, Stefanie Nachtweide, Michael A Quail, Cristina Sisu, Mario Stanke, Klara Stefflova, Cock Van Oosterhout, Frederic Veyrunes, Ben Ward, Fengtang Yang, Golbahar Yazdanifar, Amonida Zadissa, David J Adams, Alvis Brazma, Mark Gerstein, Benedict Paten, Son Pham, Thomas M Keane, Duncan T Odom, Paul Flicek,

Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus ... Read more >>

Genome Res. (Genome research)
[2018, 28(4):448-459]

Cited: 9 times

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Expression Atlas: gene and protein expression across multiple studies and organisms.

Irene Papatheodorou, Nuno A Fonseca, Maria Keays, Y Amy Tang, Elisabet Barrera, Wojciech Bazant, Melissa Burke, Anja Füllgrabe, Alfonso Muñoz-Pomer Fuentes, Nancy George, Laura Huerta, Satu Koskinen, Suhaib Mohammed, Matthew Geniza, Justin Preece, Pankaj Jaiswal, Andrew F Jarnuczak, Wolfgang Huber, Oliver Stegle, Juan Antonio Vizcaino, Alvis Brazma, Robert Petryszak,

Expression Atlas (http://www.ebi.ac.uk/gxa) is an added value database that provides information about gene and protein expression in different species and contexts, such as tissue, developmental stage, disease or cell type. The available public and controlled access data sets from different sources are curated and re-analysed using standardized, open source pipelines ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2018, 46(D1):D246-D251]

Cited: 61 times

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The BioStudies database-one stop shop for all data supporting a life sciences study.

Ugis Sarkans, Mikhail Gostev, Awais Athar, Ehsan Behrangi, Olga Melnichuk, Ahmed Ali, Jasmine Minguet, Juan Camillo Rada, Catherine Snow, Andrew Tikhonov, Alvis Brazma, Johanna McEntyre,

BioStudies (www.ebi.ac.uk/biostudies) is a new public database that organizes data from biological studies. Typically, but not exclusively, a study is associated with a publication. BioStudies offers a simple way to describe the study structure, and provides flexible data deposition tools and data access interfaces. The actual data can be stored ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2018, 46(D1):D1266-D1270]

Cited: 7 times

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clustComp, a bioconductor package for the comparison of clustering results.

Aurora Torrente, Alvis Brazma,

Summary:clustComp is an open source Bioconductor package that implements different techniques for the comparison of two gene expression clustering results. These include flat versus flat and hierarchical versus flat comparisons. The visualization of the similarities is provided by means of a bipartite graph, whose layout is heuristically optimized. Its flexibility ... Read more >>

Bioinformatics (Bioinformatics (Oxford, England))
[2017, 33(24):4001-4003]

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Germline determinants of the somatic mutation landscape in 2,642 cancer genomes

Sebastian Waszak, Grace Tiao, Bin Zhu, Tobias Rausch, Francesc Muyas, Bernardo Rodríguez-Martín, Raquel Rabionet, Sergei Yakneen, Georgia Escaramis, Yilong Li, Natalie Saini, Steven Roberts, German Demidov, Esa Pitkänen, Olivier Delaneau, Jose Maria Heredia-Genestar, Joachim Weischenfeldt, Suyash Shringarpure, Jieming Chen, Hidewaki Nakagawa, Ludmil Alexandrov, Oliver Drechsel, Jonathan Dursi, Ayellet Segre, Erik Garrison, Serap Erkek, Nina Habermann, Lara Urban, Ekta Khurana, Andy Cafferkey, Shuto Hayashi, Seiya Imoto, Lauri Aaltonen, Eva Alvarez, Adrian Baez-Ortega, Matthew Bailey, Mattia Bosio, Alicia Bruzos, Ivo Buchhalter, Carlos Bustamante, Claudia Calabrese, Anthony DiBiase, Mark Gerstein, Aliaksei Holik, Xing Hua, Kuan-lin Huang, Ivica Letunic, Leszek Klimczak, Roelof Koster, Sushant Kumar, Mike McLellan, Jay Mashl, Lisa Mirabello, Steven Newhouse, Aparna Prasad, Gunnar Rätsch, Matthias Schlesner, Roland Schwarz, Pramod Sharma, Tal Shmaya, Nikos Sidiropoulos, Lei Song, Hana Susak, Tomas Tanskanen, Marta Tojo, David Wedge, Mark Wright, Ying Wu, Kai Ye, Venkata Yellapantula, Jorge Zamora, Atul Butte, Gad Getz, Jared Simpson, Li Ding, Tomas Marques-Bonet, Arcadi Navarro, Alvis Brazma, Peter Campbell, Stephen Chanock, Nilanjan Chatterjee, Oliver Stegle, Reiner Siebert, Stephan Ossowski, Olivier Harismendy, Dmitry Gordenin, Jose MC Tubio, Francisco De La Vega, Douglas Easton, Xavier Estivill, Jan Korbel, , ,

Abstract Cancers develop through somatic mutagenesis, however germline genetic variation can markedly contribute to tumorigenesis via diverse mechanisms. We discovered and phased 88 million germline single nucleotide variants, short insertions/deletions, and large structural variants in whole genomes from 2,642 cancer patients, and employed this genomic resource to study genetic determinants ... Read more >>

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Genomic basis for RNA alterations revealed by whole-genome analyses of 27 cancer types

, Claudia Calabrese, Natalie Davidson, Nuno Fonseca, Yao He, André Kahles, Kjong-Van Lehmann, Fenglin Liu, Yuichi Shiraishi, Cameron Soulette, Lara Urban, Deniz Demircioğlu, Liliana Greger, Siliang Li, Dongbing Liu, Marc Perry, Linda Xiang, Fan Zhang, Junjun Zhang, Peter Bailey, Serap Erkek, Katherine Hoadley, Yong Hou, Helena Kilpinen, Jan Korbel, Maximillian Marin, Julia Markowski, Tannistha Nandi, Qiang Pan-Hammarström, Chandra Sekhar Pedamallu, Reiner Siebert, Stefan Stark, Hong Su, Hong Su, Patrick Tan, Sebastian Waszak, Christina Yung, Shida Zhu, Philip Awadalla, Chad Creighton, Matthew Meyerson, B.F. Francis Ouellette, Kui Wu, Huangming Yang, Alvis Brazma, Angela Brooks, Jonathan Göke, Gunnar Rätsch, Roland Schwarz, Oliver Stegle, Zemin Zhang, , ,

Abstract We present the most comprehensive catalogue of cancer-associated gene alterations through characterization of tumor transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes project. Using matched whole-genome sequencing data, we attributed RNA alterations to germline and somatic DNA alterations, revealing likely genetic mechanisms. We identified 444 associations ... Read more >>

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A Pan-Cancer Transcriptome Analysis Reveals Pervasive Regulation through Tumor-Associated Alternative Promoters

Deniz Demircioğlu, Martin Kindermans, Tannistha Nandi, Engin Cukuroglu, Claudia Calabrese, Nuno Fonseca, Andre Kahles, Kjong Lehmann, Oliver Stegle, Alvis Brazma, Angela Brooks, Gunnar Rätsch, Patrick Tan, Jonathan Göke, ,

ABSTRACT Most human protein-coding genes are regulated by multiple, distinct promoters, suggesting that the choice of promoter is as important as its level of transcriptional activity. While the role of promoters as driver elements in cancer has been recognized, the contribution of alternative promoters to regulation of the cancer transcriptome ... Read more >>

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Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes

David Thybert, Maša Roller, Fábio C.P. Navarro, Ian Fiddes, Ian Streeter, Christine Feig, David Martin-Galvez, Mikhail Kolmogorov, Václav Janoušek, Wasiu Akanni, Bronwen Aken, Sarah Aldridge, Varshith Chakrapani, William Chow, Laura Clarke, Carla Cummins, Anthony Doran, Matthew Dunn, Leo Goodstadt, Kerstin Howe, Matthew Howell, Ambre-Aurore Josselin, Robert Karn, Christina Laukaitis, Lilue Jingtao, Fergal Martin, Matthieu Muffato, Michael Quail, Cristina Sisu, Mario Stanke, Klara Stefflova, Cock Van Oosterhout, Frederic Veyrunes, Ben Ward, Fengtang Yang, Golbahar Yazdanifar, Amonida Zadissa, David Adams, Alvis Brazma, Mark Gerstein, Benedict Paten, Son Pham, Thomas Keane, Duncan Odom, Paul Flicek,

ABSTRACT Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and ... Read more >>

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