LIVIVO - Search results -

Search results

Result 1 - 10 of total 84

Search options

Article ; Online: Phenotypic noise and plasticity in cancer evolution.

Whiting, Frederick J H / Househam, Jacob / Baker, Ann-Marie / Sottoriva, Andrea / Graham, Trevor A

2023

Abstract: Non-genetic alterations can produce changes in a cell's phenotype. In cancer, these phenomena can influence a cell's fitness by conferring access to heritable, beneficial phenotypes. Herein, we argue that current discussions of 'phenotypic plasticity' in ...

Abstract	Non-genetic alterations can produce changes in a cell's phenotype. In cancer, these phenomena can influence a cell's fitness by conferring access to heritable, beneficial phenotypes. Herein, we argue that current discussions of 'phenotypic plasticity' in cancer evolution ignore a salient feature of the original definition: namely, that it occurs in response to an environmental change. We suggest 'phenotypic noise' be used to distinguish non-genetic changes in phenotype that occur independently from the environment. We discuss the conceptual and methodological techniques used to identify these phenomena during cancer evolution. We propose that the distinction will guide efforts to define mechanisms of phenotype change, accelerate translational work to manipulate phenotypes through treatment, and, ultimately, improve patient outcomes.
Language	English
Publishing date	2023-11-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	30122-x
ISSN	1879-3088 ; 0962-8924
ISSN (online)	1879-3088
ISSN	0962-8924
DOI	10.1016/j.tcb.2023.10.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.MG 25: Show issues
Zs.MO 113: Show issues
Zs.A 3410: 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)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.

Werner, Benjamin / Sottoriva, Andrea

PLoS computational biology

2018 Volume 14, Issue 6, Page(s) e1006233

Abstract: The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation ... ...

Abstract	The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99)). In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88) in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10-9/bp/division in small intestine to 1.6 × 10-7/bp/division in skin.
MeSH term(s)	Cell Proliferation ; Chromosome Segregation/genetics ; Computational Biology ; DNA/genetics ; DNA/metabolism ; DNA Replication/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Intestine, Small/metabolism ; Mutation/genetics ; Mutation Rate ; Organ Specificity ; Skin/metabolism
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2018-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1006233
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Quantification of spatial subclonal interactions enhancing the invasive phenotype of pediatric glioma.

Tari, Haider / Kessler, Ketty / Trahearn, Nick / Werner, Benjamin / Vinci, Maria / Jones, Chris / Sottoriva, Andrea

Cell reports

2022 Volume 40, Issue 9, Page(s) 111283

Abstract: Diffuse midline gliomas (DMGs) are highly aggressive, incurable childhood brain tumors. They present a clinical challenge due to many factors, including heterogeneity and diffuse infiltration, complicating disease management. Recent studies have ... ...

Abstract	Diffuse midline gliomas (DMGs) are highly aggressive, incurable childhood brain tumors. They present a clinical challenge due to many factors, including heterogeneity and diffuse infiltration, complicating disease management. Recent studies have described the existence of subclonal populations that may co-operate to drive pro-tumorigenic processes such as cellular invasion. However, a precise quantification of subclonal interactions is lacking, a problem that extends to other cancers. In this study, we combine spatial computational modeling of cellular interactions during invasion with co-evolution experiments of clonally disassembled patient-derived DMG cells. We design a Bayesian inference framework to quantify spatial subclonal interactions between molecular and phenotypically distinct lineages with different patterns of invasion. We show how this approach could discriminate genuine interactions, where one clone enhanced the invasive phenotype of another, from those apparently only due to the complex dynamics of spatially restricted growth. This study provides a framework for the quantification of subclonal interactions in DMG.
MeSH term(s)	Bayes Theorem ; Brain Neoplasms/pathology ; Carcinogenesis ; Glioma/pathology ; Humans ; Phenotype
Language	English
Publishing date	2022-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.111283
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Contribution of pks

Chen, Bingjie / Ramazzotti, Daniele / Heide, Timon / Spiteri, Inmaculada / Fernandez-Mateos, Javier / James, Chela / Magnani, Luca / Graham, Trevor A / Sottoriva, Andrea

Nature communications

2023 Volume 14, Issue 1, Page(s) 7827

Abstract: The dominant mutational signature in colorectal cancer genomes is C > T deamination (COSMIC Signature 1) and, in a small subgroup, mismatch repair signature (COSMIC signatures 6 and 44). Mutations in common colorectal cancer driver genes are often not ... ...

Abstract	The dominant mutational signature in colorectal cancer genomes is C > T deamination (COSMIC Signature 1) and, in a small subgroup, mismatch repair signature (COSMIC signatures 6 and 44). Mutations in common colorectal cancer driver genes are often not consistent with those signatures. Here we perform whole-genome sequencing of normal colon crypts from cancer patients, matched to a previous multi-omic tumour dataset. We analyse normal crypts that were distant vs adjacent to the cancer. In contrast to healthy individuals, normal crypts of colon cancer patients have a high incidence of pks + (polyketide synthases) E.coli (Escherichia coli) mutational and indel signatures, and this is confirmed by metagenomics. These signatures are compatible with many clonal driver mutations detected in the corresponding cancer samples, including in chromatin modifier genes, supporting their role in early tumourigenesis. These results provide evidence that pks + E.coli is a potential driver of carcinogenesis in the human gut.
MeSH term(s)	Humans ; Escherichia coli/genetics ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Mutation ; Carcinogenesis/genetics ; Colonic Neoplasms
Language	English
Publishing date	2023-11-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43329-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Author Correction: Resolving genetic heterogeneity in cancer.

Turajlic, Samra / Sottoriva, Andrea / Graham, Trevor / Swanton, Charles

Nature reviews. Genetics

2019 Volume 21, Issue 1, Page(s) 65

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Language	English
Publishing date	2019-01-10
Publishing country	England
Document type	Published Erratum
ZDB-ID	2035157-4
ISSN	1471-0064 ; 1471-0056
ISSN (online)	1471-0064
ISSN	1471-0056
DOI	10.1038/s41576-019-0188-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5474: 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 40: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Resolving genetic heterogeneity in cancer.

Turajlic, Samra / Sottoriva, Andrea / Graham, Trevor / Swanton, Charles

Nature reviews. Genetics

2019 Volume 20, Issue 7, Page(s) 404–416

Abstract: To a large extent, cancer conforms to evolutionary rules defined by the rates at which clones mutate, adapt and grow. Next-generation sequencing has provided a snapshot of the genetic landscape of most cancer types, and cancer genomics approaches are ... ...

Abstract	To a large extent, cancer conforms to evolutionary rules defined by the rates at which clones mutate, adapt and grow. Next-generation sequencing has provided a snapshot of the genetic landscape of most cancer types, and cancer genomics approaches are driving new insights into cancer evolutionary patterns in time and space. In contrast to species evolution, cancer is a particular case owing to the vast size of tumour cell populations, chromosomal instability and its potential for phenotypic plasticity. Nevertheless, an evolutionary framework is a powerful aid to understand cancer progression and therapy failure. Indeed, such a framework could be applied to predict individual tumour behaviour and support treatment strategies.
MeSH term(s)	Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Chromosomal Instability ; Clonal Evolution ; Clone Cells ; DNA Copy Number Variations ; Genetic Heterogeneity ; Genomics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Models, Genetic ; Neoplasm Metastasis ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplastic Cells, Circulating/metabolism ; Neoplastic Cells, Circulating/pathology ; Selection, Genetic ; Single-Cell Analysis
Language	English
Publishing date	2019-03-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2035157-4
ISSN	1471-0064 ; 1471-0056
ISSN (online)	1471-0064
ISSN	1471-0056
DOI	10.1038/s41576-019-0114-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5474: 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 40: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Measuring Clonal Evolution in Cancer with Genomics.

Williams, Marc J / Sottoriva, Andrea / Graham, Trevor A

Annual review of genomics and human genetics

2019 Volume 20, Page(s) 309–329

Abstract: Cancers originate from somatic cells in the human body that have accumulated genetic alterations. These mutations modify the phenotype of the cells, allowing them to escape the homeostatic regulation that maintains normal cell number. Viewed through the ... ...

Abstract	Cancers originate from somatic cells in the human body that have accumulated genetic alterations. These mutations modify the phenotype of the cells, allowing them to escape the homeostatic regulation that maintains normal cell number. Viewed through the lens of evolutionary biology, the transformation of normal cells into malignant cells is evolution in action. Evolution continues throughout cancer growth, progression, treatment resistance, and disease relapse, driven by adaptation to changes in the cancer's environment, and intratumor heterogeneity is an inevitable consequence of this evolutionary process. Genomics provides a powerful means to characterize tumor evolution, enabling quantitative measurement of evolving clones across space and time. In this review, we discuss concepts and approaches to quantify and measure this evolutionary process in cancer using genomics.
MeSH term(s)	Clonal Evolution ; Genomics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Models, Genetic ; Mutation ; Neoplasms/genetics ; Neoplasms/physiopathology ; Sequence Analysis, DNA
Language	English
Publishing date	2019-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2037670-4
ISSN	1545-293X ; 1527-8204
ISSN (online)	1545-293X
ISSN	1527-8204
DOI	10.1146/annurev-genom-083117-021712
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Se 2016: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.

Benjamin Werner / Andrea Sottoriva

PLoS Computational Biology, Vol 14, Iss 6, p e

2018 Volume 1006233

Abstract	The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99)). In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88) in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10-9/bp/division in small intestine to 1.6 × 10-7/bp/division in skin.
Keywords	Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The MOBSTER R package for tumour subclonal deconvolution from bulk DNA whole-genome sequencing data.

Caravagna, Giulio / Sanguinetti, Guido / Graham, Trevor A / Sottoriva, Andrea

BMC bioinformatics

2020 Volume 21, Issue 1, Page(s) 531

Abstract: Background: The large-scale availability of whole-genome sequencing profiles from bulk DNA sequencing of cancer tissues is fueling the application of evolutionary theory to cancer. From a bulk biopsy, subclonal deconvolution methods are used to ... ...

Abstract	Background: The large-scale availability of whole-genome sequencing profiles from bulk DNA sequencing of cancer tissues is fueling the application of evolutionary theory to cancer. From a bulk biopsy, subclonal deconvolution methods are used to determine the composition of cancer subpopulations in the biopsy sample, a fundamental step to determine clonal expansions and their evolutionary trajectories. Results: In a recent work we have developed a new model-based approach to carry out subclonal deconvolution from the site frequency spectrum of somatic mutations. This new method integrates, for the first time, an explicit model for neutral evolutionary forces that participate in clonal expansions; in that work we have also shown that our method improves largely over competing data-driven methods. In this Software paper we present mobster, an open source R package built around our new deconvolution approach, which provides several functions to plot data and fit models, assess their confidence and compute further evolutionary analyses that relate to subclonal deconvolution. Conclusions: We present the mobster package for tumour subclonal deconvolution from bulk sequencing, the first approach to integrate Machine Learning and Population Genetics which can explicitly model co-existing neutral and positive selection in cancer. We showcase the analysis of two datasets, one simulated and one from a breast cancer patient, and overview all package functionalities.
MeSH term(s)	Breast Neoplasms/genetics ; Cell Proliferation ; Clone Cells ; DNA, Neoplasm/genetics ; Data Analysis ; Female ; Genetics, Population ; Humans ; Machine Learning ; Models, Genetic ; Mutation/genetics ; Software ; Whole Genome Sequencing
Chemical Substances	DNA, Neoplasm
Language	English
Publishing date	2020-11-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-020-03863-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Contribution of pks + E. coli mutations to colorectal carcinogenesis

Bingjie Chen / Daniele Ramazzotti / Timon Heide / Inmaculada Spiteri / Javier Fernandez-Mateos / Chela James / Luca Magnani / Trevor A. Graham / Andrea Sottoriva

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 9

Abstract: Abstract The dominant mutational signature in colorectal cancer genomes is C > T deamination (COSMIC Signature 1) and, in a small subgroup, mismatch repair signature (COSMIC signatures 6 and 44). Mutations in common colorectal cancer driver genes are ... ...

Abstract	Abstract The dominant mutational signature in colorectal cancer genomes is C > T deamination (COSMIC Signature 1) and, in a small subgroup, mismatch repair signature (COSMIC signatures 6 and 44). Mutations in common colorectal cancer driver genes are often not consistent with those signatures. Here we perform whole-genome sequencing of normal colon crypts from cancer patients, matched to a previous multi-omic tumour dataset. We analyse normal crypts that were distant vs adjacent to the cancer. In contrast to healthy individuals, normal crypts of colon cancer patients have a high incidence of pks + (polyketide synthases) E.coli (Escherichia coli) mutational and indel signatures, and this is confirmed by metagenomics. These signatures are compatible with many clonal driver mutations detected in the corresponding cancer samples, including in chromatin modifier genes, supporting their role in early tumourigenesis. These results provide evidence that pks + E.coli is a potential driver of carcinogenesis in the human gut.
Keywords	Science ; Q
Subject code	616
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED