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Article ; Online: Removing unwanted variation with CytofRUV to integrate multiple CyTOF datasets.

Trussart, Marie / Teh, Charis E / Tan, Tania / Leong, Lawrence / Gray, Daniel Hd / Speed, Terence P

2020 Volume 9

Abstract: Mass cytometry (CyTOF) is a technology that has revolutionised single-cell biology. By detecting over 40 proteins on millions of single cells, CyTOF allows the characterisation of cell subpopulations in unprecedented detail. However, most CyTOF studies ... ...

Abstract	Mass cytometry (CyTOF) is a technology that has revolutionised single-cell biology. By detecting over 40 proteins on millions of single cells, CyTOF allows the characterisation of cell subpopulations in unprecedented detail. However, most CyTOF studies require the integration of data from multiple CyTOF batches usually acquired on different days and possibly at different sites. To date, the integration of CyTOF datasets remains a challenge due to technical differences arising in multiple batches. To overcome this limitation, we developed an approach called CytofRUV for analysing multiple CyTOF batches, which includes an R-Shiny application with diagnostic plots. CytofRUV can correct for batch effects and integrate data from large numbers of patients and conditions across batches, to confidently compare cellular changes and correlate these with clinically relevant outcomes.
MeSH term(s)	Algorithms ; Cluster Analysis ; Computational Biology/methods ; Databases, Factual ; Flow Cytometry ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Leukocytes, Mononuclear/cytology ; Mass Spectrometry ; Single-Cell Analysis ; Software
Language	English
Publishing date	2020-09-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.59630
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Article ; Online: sccomp: Robust differential composition and variability analysis for single-cell data.

Mangiola, Stefano / Roth-Schulze, Alexandra J / Trussart, Marie / Zozaya-Valdés, Enrique / Ma, Mengyao / Gao, Zijie / Rubin, Alan F / Speed, Terence P / Shim, Heejung / Papenfuss, Anthony T

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 33, Page(s) e2203828120

Abstract: Cellular omics such as single-cell genomics, proteomics, and microbiomics allow the characterization of tissue and microbial community composition, which can be compared between conditions to identify biological drivers. This strategy has been critical ... ...

Abstract	Cellular omics such as single-cell genomics, proteomics, and microbiomics allow the characterization of tissue and microbial community composition, which can be compared between conditions to identify biological drivers. This strategy has been critical to revealing markers of disease progression, such as cancer and pathogen infection. A dedicated statistical method for differential variability analysis is lacking for cellular omics data, and existing methods for differential composition analysis do not model some compositional data properties, suggesting there is room to improve model performance. Here, we introduce sccomp, a method for differential composition and variability analyses that jointly models data count distribution, compositionality, group-specific variability, and proportion mean-variability association, being aware of outliers. sccomp provides a comprehensive analysis framework that offers realistic data simulation and cross-study knowledge transfer. Here, we demonstrate that mean-variability association is ubiquitous across technologies, highlighting the inadequacy of the very popular Dirichlet-multinomial distribution. We show that sccomp accurately fits experimental data, significantly improving performance over state-of-the-art algorithms. Using sccomp, we identified differential constraints and composition in the microenvironment of primary breast cancer.
MeSH term(s)	Genomics ; Proteomics/methods ; Computer Simulation ; Microbiota ; Algorithms
Language	English
Publishing date	2023-08-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2203828120
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Zs.A 1148: Show issues

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Article ; Online: Identification of aberrant luminal progenitors and mTORC1 as a potential breast cancer prevention target in BRCA2 mutation carriers.

Nature cell biology

2024 Volume 26, Issue 1, Page(s) 138–152

Abstract: Inheritance of a BRCA2 pathogenic variant conveys a substantial life-time risk of breast cancer. Identification of the cell(s)-of-origin of BRCA2-mutant breast cancer and targetable perturbations that contribute to transformation remains an unmet need ... ...

Abstract	Inheritance of a BRCA2 pathogenic variant conveys a substantial life-time risk of breast cancer. Identification of the cell(s)-of-origin of BRCA2-mutant breast cancer and targetable perturbations that contribute to transformation remains an unmet need for these individuals who frequently undergo prophylactic mastectomy. Using preneoplastic specimens from age-matched, premenopausal females, here we show broad dysregulation across the luminal compartment in BRCA2
MeSH term(s)	Female ; Humans ; Breast Neoplasms/genetics ; Breast Neoplasms/prevention & control ; Mastectomy ; Mutation ; BRCA2 Protein/genetics ; Carcinogenesis ; Cell Transformation, Neoplastic ; BRCA1 Protein/genetics
Chemical Substances	BRCA2 Protein ; BRCA1 Protein ; BRCA2 protein, human
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-023-01315-5
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Zs.A 5169: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Assessing the limits of restraint-based 3D modeling of genomes and genomic domains.

Trussart, Marie / Serra, François / Baù, Davide / Junier, Ivan / Serrano, Luís / Marti-Renom, Marc A

Nucleic acids research

2015 Volume 43, Issue 7, Page(s) 3465–3477

Abstract: Restraint-based modeling of genomes has been recently explored with the advent of Chromosome Conformation Capture (3C-based) experiments. We previously developed a reconstruction method to resolve the 3D architecture of both prokaryotic and eukaryotic ... ...

Abstract	Restraint-based modeling of genomes has been recently explored with the advent of Chromosome Conformation Capture (3C-based) experiments. We previously developed a reconstruction method to resolve the 3D architecture of both prokaryotic and eukaryotic genomes using 3C-based data. These models were congruent with fluorescent imaging validation. However, the limits of such methods have not systematically been assessed. Here we propose the first evaluation of a mean-field restraint-based reconstruction of genomes by considering diverse chromosome architectures and different levels of data noise and structural variability. The results show that: first, current scoring functions for 3D reconstruction correlate with the accuracy of the models; second, reconstructed models are robust to noise but sensitive to structural variability; third, the local structure organization of genomes, such as Topologically Associating Domains, results in more accurate models; fourth, to a certain extent, the models capture the intrinsic structural variability in the input matrices and fifth, the accuracy of the models can be a priori predicted by analyzing the properties of the interaction matrices. In summary, our work provides a systematic analysis of the limitations of a mean-field restrain-based method, which could be taken into consideration in further development of methods as well as their applications.
MeSH term(s)	Genome ; Models, Genetic
Language	English
Publishing date	2015-03-23
Publishing country	England
Document type	Journal Article ; Validation Study
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkv221
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Zs.A 1067: Show issues

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Article ; Online: Venetoclax treatment in patients with cancer has limited impact on circulating T and NK cells.

Teh, Charis E / Peng, Hongke / Luo, Meng-Xiao / Tan, Tania / Trussart, Marie / Howson, Lauren J / Chua, Chong Chyn / Muttiah, Christine / Brown, Fiona / Ritchie, Matthew E / Wei, Andrew H / Roberts, Andrew W / Bryant, Vanessa L / Anderson, Mary Ann / Lindeman, Geoffrey J / Huang, David C S / Thijssen, Rachel / Gray, Daniel H D

Blood advances

2022 Volume 7, Issue 12, Page(s) 2733–2745

Abstract: Venetoclax is an effective treatment for certain blood cancers, such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, most patients relapse while on venetoclax and further treatment options are limited. Combining ... ...

Abstract	Venetoclax is an effective treatment for certain blood cancers, such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, most patients relapse while on venetoclax and further treatment options are limited. Combining venetoclax with immunotherapies is an attractive approach; however, a detailed understanding of how venetoclax treatment impacts normal immune cells in patients is lacking. In this study, we performed deep profiling of peripheral blood (PB) cells from patients with CLL and AML before and after short-term treatment with venetoclax using mass cytometry (cytometry by time of flight) and found no impact on the concentrations of key T-cell subsets or their expression of checkpoint molecules. We also analyzed PB from patients with breast cancer receiving venetoclax long-term using a single-cell multiomics approach (cellular indexing of transcriptomes and epitopes by sequencing) and functional assays. We found significant depletion of B-cell populations with low expression of MCL-1 relative to other immune cells, attended by extensive transcriptomic changes. By contrast, there was less impact on circulating T cells and natural killer (NK) cells, with no changes in their subset composition, transcriptome, or function following venetoclax treatment. Our data indicate that venetoclax has minimal impact on circulating T or NK cells, supporting the rationale of combining this BH3 mimetic drug with cancer immunotherapies for more durable antitumor responses.
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Killer Cells, Natural ; Leukemia, Myeloid, Acute/drug therapy ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use
Chemical Substances	venetoclax (N54AIC43PW) ; Bridged Bicyclo Compounds, Heterocyclic
Language	English
Publishing date	2022-12-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022008221
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Article ; Online: Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer.

Weeden, Clare E / Gayevskiy, Velimir / Marceaux, Claire / Batey, Daniel / Tan, Tania / Yokote, Kenta / Ribera, Nina Tubau / Clatch, Allison / Christo, Susan / Teh, Charis E / Mitchell, Andrew J / Trussart, Marie / Rankin, Lucille / Obers, Andreas / McDonald, Jackson A / Sutherland, Kate D / Sharma, Varun J / Starkey, Graham / D'Costa, Rohit /

Antippa, Phillip / Leong, Tracy / Steinfort, Daniel / Irving, Louis / Swanton, Charles / Gordon, Claire L / Mackay, Laura K / Speed, Terence P / Gray, Daniel H D / Asselin-Labat, Marie-Liesse

Cancer cell

2023 Volume 41, Issue 5, Page(s) 837–852.e6

Abstract: Tissue-resident memory T ( ... ...

Abstract	Tissue-resident memory T (T
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism ; Memory T Cells ; Immunologic Memory ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung ; CD8-Positive T-Lymphocytes
Language	English
Publishing date	2023-04-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2023.03.019
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Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 104: Show issues

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Article ; Online: Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters.

Jansz, Natasha / Keniry, Andrew / Trussart, Marie / Bildsoe, Heidi / Beck, Tamara / Tonks, Ian D / Mould, Arne W / Hickey, Peter / Breslin, Kelsey / Iminitoff, Megan / Ritchie, Matthew E / McGlinn, Edwina / Kay, Graham F / Murphy, James M / Blewitt, Marnie E

Nature structural & molecular biology

2018 Volume 25, Issue 9, Page(s) 766–777

Abstract: The regulation of higher-order chromatin structure is complex and dynamic, and a full understanding of the suite of mechanisms governing this architecture is lacking. Here, we reveal the noncanonical SMC protein Smchd1 to be a novel regulator of long- ... ...

Abstract	The regulation of higher-order chromatin structure is complex and dynamic, and a full understanding of the suite of mechanisms governing this architecture is lacking. Here, we reveal the noncanonical SMC protein Smchd1 to be a novel regulator of long-range chromatin interactions in mice, and we add Smchd1 to the canon of epigenetic proteins required for Hox-gene regulation. The effect of losing Smchd1-dependent chromatin interactions has varying outcomes that depend on chromatin context. At autosomal targets transcriptionally sensitive to Smchd1 deletion, we found increased short-range interactions and ectopic enhancer activation. In contrast, the inactive X chromosome was transcriptionally refractive to Smchd1 ablation, despite chromosome-wide increases in short-range interactions. In the inactive X, we observed spreading of trimethylated histone H3 K27 (H3K27me3) domains into regions not normally decorated by this mark. Together, these data suggest that Smchd1 is able to insulate chromatin, thereby limiting access to other chromatin-modifying proteins.
MeSH term(s)	Animals ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/physiology ; Enhancer Elements, Genetic ; Gene Deletion ; Gene Silencing ; Genes, Homeobox ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Multigene Family ; X Chromosome
Chemical Substances	Chromatin ; Chromosomal Proteins, Non-Histone ; SmcHD1 protein, mouse
Language	English
Publishing date	2018-08-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126708-X
ISSN	1545-9985 ; 1545-9993
ISSN (online)	1545-9985
ISSN	1545-9993
DOI	10.1038/s41594-018-0111-z
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Zs.A 4101: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Defined chromosome structure in the genome-reduced bacterium Mycoplasma pneumoniae.

Trussart, Marie / Yus, Eva / Martinez, Sira / Baù, Davide / Tahara, Yuhei O / Pengo, Thomas / Widjaja, Michael / Kretschmer, Simon / Swoger, Jim / Djordjevic, Steven / Turnbull, Lynne / Whitchurch, Cynthia / Miyata, Makoto / Marti-Renom, Marc A / Lluch-Senar, Maria / Serrano, Luís

Nature communications

2017 Volume 8, Page(s) 14665

Abstract: DNA-binding proteins are central regulators of chromosome organization; however, in genome-reduced bacteria their diversity is largely diminished. Whether the chromosomes of such bacteria adopt defined three-dimensional structures remains unexplored. ... ...

Abstract	DNA-binding proteins are central regulators of chromosome organization; however, in genome-reduced bacteria their diversity is largely diminished. Whether the chromosomes of such bacteria adopt defined three-dimensional structures remains unexplored. Here we combine Hi-C and super-resolution microscopy to determine the structure of the Mycoplasma pneumoniae chromosome at a 10 kb resolution. We find a defined structure, with a global symmetry between two arms that connect opposite poles, one bearing the chromosomal Ori and the other the midpoint. Analysis of local structures at a 3 kb resolution indicates that the chromosome is organized into domains ranging from 15 to 33 kb. We provide evidence that genes within the same domain tend to be co-regulated, suggesting that chromosome organization influences transcriptional regulation, and that supercoiling regulates local organization. This study extends the current understanding of bacterial genome organization and demonstrates that a defined chromosomal structure is a universal feature of living systems.
MeSH term(s)	Chromosome Structures ; Chromosomes, Bacterial/ultrastructure ; DNA, Bacterial/ultrastructure ; DNA, Superhelical/ultrastructure ; Gene Expression Regulation, Bacterial ; Genome, Bacterial/genetics ; Microscopy ; Molecular Conformation ; Mycoplasma pneumoniae/genetics ; Mycoplasma pneumoniae/ultrastructure ; Nucleic Acid Conformation
Chemical Substances	DNA, Bacterial ; DNA, Superhelical
Language	English
Publishing date	2017-03-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/ncomms14665
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