141 Works

Data from: Origins of lymphatic and distant metastases in human colorectal cancer

Kamila Naxerova, Johannes G. Reiter, Elena Brachtel, Jochen K. Lennerz, Marc Van De Wetering, Andrew Rowan, Tianxi Cai, Hans Clevers, Charles Swanton, Martin A. Nowak, Stephen J. Elledge & Rakesh K. Jain
The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal...

Data from: Genome-wide evolutionary dynamics of influenza B viruses on a global scale

Pinky Langat, Jayna Raghwani, Gytis Dudas, Thomas A. Bowden, Stephanie Edwards, Astrid Gall, Trevor Bedford, Andrew Rambaut, Rodney S. Daniels, Colin A. Russell, Oliver G. Pybus, John McCauley, Paul Kellam & Simon J. Watson
The global-scale epidemiology and genome-wide evolutionary dynamics of influenza B remain poorly understood compared with influenza A viruses. We compiled a spatio-temporally comprehensive dataset of influenza B viruses, comprising over 2,500 genomes sampled worldwide between 1987 and 2015, including 382 newly-sequenced genomes that fill substantial gaps in previous molecular surveillance studies. Our contributed data increase the number of available influenza B virus genomes in Europe, Africa and Central Asia, improving the global context to study...

Imaging mass cytometry data: Head and neck squamous cell carcinoma tissue section

Jessica Timms, James Opzoomer, Kevin Blighe, Thanos Mourikis, Nicolas Chapuis, Richard Bekoe, Sedigeh Kareemaghay, Paola Nocerino, Mahvash Tavassoli, Claire Harrison, Francesca Ciccarelli, Peter Parker, James Arnold, Benedetta Apollonio, Alan Ramsay, Michaela Fontenay, Paul Barber, James Arnold & Shahram Kordasti
High dimensional cytometry is an innovative tool for immune monitoring in health and disease, it has provided novel insight into the underlying biology as well as biomarkers for a variety of diseases. However, the analysis of multiparametric “big data” usually requires specialist computational knowledge. Here we describe ImmunoCluster (https://github.com/kordastilab/ImmunoCluster) an R package for immune profiling cellular heterogeneity in high dimensional liquid and imaging mass cytometry, and flow cytometry data, designed to facilitate computational analysis by...

Additional file 3 of Probing SARS-CoV-2-positive plasma to identify potential factors correlating with mild COVID-19 in Ghana, West Africa

Kesego Tapela, Fatima O. Oyawoye, Charles Ochieng’ Olwal, Precious C. Opurum, Jones Amo Amponsah, Kekeli Aku Lumor Segbedzi, Becky Tetteh, Frederick Kumi-Ansah, Joe K. Mutungi, Evangeline Obodai, Emmanuella Amoako, Seth Agyemang, Nicaise Tuikue Ndam, William Kwabena Ampofo, Julian C. Rayner, Gordon A. Awandare, Lily Paemka, Yaw Bediako & Peter Kojo Quashie
Additional file 3. Antibody profiles among SARS-CoV-2 infected patients. A: The kinetics of IgG in asymptomatic individuals (n = 3) in response to SARS-CoV-2. Data represents the quantity of the multiple time points of the cytokines, B: Differential expression levels of IgG against SARS-CoV-2 spike and nucleocapsid proteins in symptomatic in response to COVID-19. Data represents the median quantity with the 25th and 75th percentiles.

Additional file 2 of Probing SARS-CoV-2-positive plasma to identify potential factors correlating with mild COVID-19 in Ghana, West Africa

Kesego Tapela, Fatima O. Oyawoye, Charles Ochieng’ Olwal, Precious C. Opurum, Jones Amo Amponsah, Kekeli Aku Lumor Segbedzi, Becky Tetteh, Frederick Kumi-Ansah, Joe K. Mutungi, Evangeline Obodai, Emmanuella Amoako, Seth Agyemang, Nicaise Tuikue Ndam, William Kwabena Ampofo, Julian C. Rayner, Gordon A. Awandare, Lily Paemka, Yaw Bediako & Peter Kojo Quashie
Additional file 2. Change on cytokine concentration levels over time in COVID-19 positive individuals. The cytokine concentration levels analysed from plasma of COVID-19 asymptomatic (n = 3), monthly for four months. The quantity of the cytokines for each sampling month is shown by the line graph.

Additional file 5 of Probing SARS-CoV-2-positive plasma to identify potential factors correlating with mild COVID-19 in Ghana, West Africa

Kesego Tapela, Fatima O. Oyawoye, Charles Ochieng’ Olwal, Precious C. Opurum, Jones Amo Amponsah, Kekeli Aku Lumor Segbedzi, Becky Tetteh, Frederick Kumi-Ansah, Joe K. Mutungi, Evangeline Obodai, Emmanuella Amoako, Seth Agyemang, Nicaise Tuikue Ndam, William Kwabena Ampofo, Julian C. Rayner, Gordon A. Awandare, Lily Paemka, Yaw Bediako & Peter Kojo Quashie
Additional file 5. The half-life of cytokines in asymptomatic and symptomatic patients. The cytokine concentration levels were for cytokines with significant difference between symptomatic and asymptomatic cases (14 cytokines), pro-inflammatory, anti-inflammatory and chemokines. The median half-life of the cytokines is shown by a horizontal line across the dot plot while the lower and upper dotted lines represent the 25th and 75th percentiles, respectively. Statistical significance between symptomatic and asymptomatic patients were determined by Mann-Whitney test...

Additional file 8 of Probing SARS-CoV-2-positive plasma to identify potential factors correlating with mild COVID-19 in Ghana, West Africa

Kesego Tapela, Fatima O. Oyawoye, Charles Ochieng’ Olwal, Precious C. Opurum, Jones Amo Amponsah, Kekeli Aku Lumor Segbedzi, Becky Tetteh, Frederick Kumi-Ansah, Joe K. Mutungi, Evangeline Obodai, Emmanuella Amoako, Seth Agyemang, Nicaise Tuikue Ndam, William Kwabena Ampofo, Julian C. Rayner, Gordon A. Awandare, Lily Paemka, Yaw Bediako & Peter Kojo Quashie
Additional file 8: Table S1. The median cytokine levels of healthy individuals (n = 124). Table S2. Heathy control samples used in the study.

Additional file 1 of A genetic model for central chondrosarcoma evolution correlates with patient outcome

William Cross, Iben Lyskjær, Tom Lesluyes, Steven Hargreaves, Anna-Christina Strobl, Christopher Davies, Sara Waise, Shadi Hames-Fathi, Dahmane Oukrif, Hongtao Ye, Fernanda Amary, Roberto Tirabosco, Craig Gerrand, Toby Baker, David Barnes, Christopher Steele, Ludmil Alexandrov, Gareth Bond, Paul Cool, Nischalan Pillay, Peter Van Loo & Adrienne M. Flanagan
Additional file 1: Supplementary Tables 1-6.

Additional file 3 of A genetic model for central chondrosarcoma evolution correlates with patient outcome

William Cross, Iben Lyskjær, Tom Lesluyes, Steven Hargreaves, Anna-Christina Strobl, Christopher Davies, Sara Waise, Shadi Hames-Fathi, Dahmane Oukrif, Hongtao Ye, Fernanda Amary, Roberto Tirabosco, Craig Gerrand, Toby Baker, David Barnes, Christopher Steele, Ludmil Alexandrov, Gareth Bond, Paul Cool, Nischalan Pillay, Peter Van Loo & Adrienne M. Flanagan
Additional file 3: Supplementary Figs. 1-8, Notes 1-3.

Additional file 1 of A genetic model for central chondrosarcoma evolution correlates with patient outcome

William Cross, Iben Lyskjær, Tom Lesluyes, Steven Hargreaves, Anna-Christina Strobl, Christopher Davies, Sara Waise, Shadi Hames-Fathi, Dahmane Oukrif, Hongtao Ye, Fernanda Amary, Roberto Tirabosco, Craig Gerrand, Toby Baker, David Barnes, Christopher Steele, Ludmil Alexandrov, Gareth Bond, Paul Cool, Nischalan Pillay, Peter Van Loo & Adrienne M. Flanagan
Additional file 1: Supplementary Tables 1-6.

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Annika Fendler, Scott TC Shepherd, Lewis Au, Mary Wu, Ruth Harvey, Katalin A Wilkinson, Andreas M Schmitt, Zayd Tippu, Benjamin Shum, Sheima Farag, Aljosja Rogiers, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Daqi Deng … & Samra Turajlic
Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against...

Additional file 1 of Replication stress generates distinctive landscapes of DNA copy number alterations and chromosome scale losses

Nadeem Shaikh, Alice Mazzagatti, Simone De Angelis, Sarah C. Johnson, Bjorn Bakker, Diana C. J. Spierings, René Wardenaar, Eleni Maniati, Jun Wang, Michael A. Boemo, Floris Foijer & Sarah E. McClelland
Additional file 1. Contains supplementary Figs S1-S8.

Additional file 5 of Replication stress generates distinctive landscapes of DNA copy number alterations and chromosome scale losses

Nadeem Shaikh, Alice Mazzagatti, Simone De Angelis, Sarah C. Johnson, Bjorn Bakker, Diana C. J. Spierings, René Wardenaar, Eleni Maniati, Jun Wang, Michael A. Boemo, Floris Foijer & Sarah E. McClelland
Additional file 5. Review history.

A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signalling in calcium-induced Toxoplasma gondii egress.

Stephanie D Nofal, Caia Dominicus, Malgorzata Broncel, Nicholas J Katris, Helen R Flynn, Gustavo Arrizabalaga, Cyrille Y Botté, Brandon M Invergo & Moritz Treeck
Fundamental processes that govern the lytic cycle of the intracellular parasite Toxoplasma gondii are regulated by several signalling pathways. However, how these pathways are connected remains largely unknown. Here, we compare the phospho-signalling networks during Toxoplasma egress from its host cell by artificially raising cGMP or calcium levels. We show that both egress inducers trigger indistinguishable signalling responses and provide evidence for a positive feedback loop linking calcium and cyclic nucleotide signalling. Using WT and...

Supp Fig 4F Zeo + ATM ATR inhibitors

Jingkun Zeng, Stephanie Hills, Eiko Ozono & John Diffley
western blot

Supp Fig 5B RPE1 and p53KO CycE damage

Jingkun Zeng, Eiko Ozono, Stephanie Hills & John Diffley
western blot

Supp Fig 5A RPE1 p53KO validation blot

Jingkun Zeng & Stephanie Hills
western blot

Supp Fig 1D Fbxw7 KD oncogenes

Jingkun Zeng, Eiko Ozono, John Diffley & Stephanie Hills
western blot

Figure 2B Damage blot

Jingkun Zeng, Stephanie Hills, Eiko Ozono & John Diffley
western blot

Cyclin E-Induced Replicative Stress Drives p53-dependent Mitotic Bypass and Whole Genome Duplication

Jingkun Zeng, Stephanie Hills, John Diffley & Eiko Ozono
Collection of western blot data in Cyclin E-Induced Replicative Stress Drives p53-dependent Mitotic Bypass and Whole Genome Duplication

Additional file 1 of Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial

Thomas Maitre, Maryline Bonnet, Alexandra Calmy, Mihaja Raberahona, Rivonirina Andry Rakotoarivelo, Niaina Rakotosamimanana, Juan Ambrosioni, José M. Miró, Pierre Debeaudrap, Conrad Muzoora, Angharad Davis, Graeme Meintjes, Sean Wasserman, Robert Wilkinson, Serge Eholié, Frédéric Ello Nogbou, Maria-Camilla Calvo-Cortes, Corine Chazallon, Vanessa Machault, Xavier Anglaret & Fabrice Bonnet
Additional file 1. Modified MARAIS Score (modified from Marais et al. [27]).

Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial

Thomas Maitre, Maryline Bonnet, Alexandra Calmy, Mihaja Raberahona, Rivonirina Andry Rakotoarivelo, Niaina Rakotosamimanana, Juan Ambrosioni, José M. Miró, Pierre Debeaudrap, Conrad Muzoora, Angharad Davis, Graeme Meintjes, Sean Wasserman, Robert Wilkinson, Serge Eholié, Frédéric Ello Nogbou, Maria-Camilla Calvo-Cortes, Corine Chazallon, Vanessa Machault, Xavier Anglaret & Fabrice Bonnet
Abstract Background Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB), particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-co-infected patients. To reduce TBM-induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using oral high-dose rifampicin (35 mg/kg daily) and linezolid (1200 mg daily and...

MEDICC2: whole-genome doubling aware copy-number phylogenies for cancer evolution

Tom L. Kaufmann, Marina Petkovic, Thomas B. K. Watkins, Emma C. Colliver, Sofya Laskina, Nisha Thapa, Darlan C. Minussi, Nicholas Navin, Charles Swanton, Peter Van Loo, Kerstin Haase, Maxime Tarabichi & Roland F. Schwarz
Abstract Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events....

Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression.

Shaolong Cao, Jennifer R Wang, Shuangxi Ji, Peng Yang, Yaoyi Dai, Shuai Guo, Matthew D Montierth, John Paul Shen, Xiao Zhao, Jingxiao Chen, Jaewon James Lee, Paola A Guerrero, Nicholas Spetsieris, Nikolai Engedal, Sinja Taavitsainen, Kaixian Yu, Julie Livingstone, Vinayak Bhandari, Shawna M Hubert, Najat C Daw, P Andrew Futreal, Eleni Efstathiou, Bora Lim, Andrea Viale, Jianjun Zhang … & Wenyi Wang
Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimated through transcriptomic/genomic deconvolution. We estimate and validate TmS in 6,590 patient tumors across 15 cancer types, identifying...

Electron cryotomography of SARS-CoV-2 virions reveals cylinder-shaped particles with a double layer RNP assembly

Lesley J Calder, Thomas Calcraft, Saira Hussain, Ruth Harvey & Peter B Rosenthal
SARS-CoV-2 is a lipid-enveloped Betacoronavirus and cause of the Covid-19 pandemic. To study the three-dimensional architecture of the virus, we perform electron cryotomography (cryo-ET) on SARS-Cov-2 virions and three variants revealing particles of regular cylindrical morphology. The ribonucleoprotein particles packaging the genome in the virion interior form a dense, double layer assembly with a cylindrical shape related to the overall particle morphology. This organisation suggests structural interactions important to virus assembly.

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Affiliations

  • The Francis Crick Institute
    141
  • University College London
    36
  • University of Cambridge
    31
  • University of Paris
    24
  • Wellcome Sanger Institute
    19
  • Noguchi Memorial Institute for Medical Research
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  • University of Ghana
    18
  • University of Cape Coast
    18
  • Chengdu University of Traditional Chinese Medicine
    13
  • Tianjin Medical University General Hospital
    11