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  1. Article ; Online: A Countable-Type Branching Process Model for the Tug-of-War Cancer Cell Dynamics.

    Wang, Ren-Yi / Kimmel, Marek

    Bulletin of mathematical biology

    2024  Volume 86, Issue 2, Page(s) 18

    Abstract: We consider a time-continuous Markov branching process of proliferating cells with a countable collection of types. Among-type transitions are inspired by the Tug-of-War process introduced by McFarland et al. (Proc Natl Acad Sci 111(42):15138-15143, 2014) ...

    Abstract We consider a time-continuous Markov branching process of proliferating cells with a countable collection of types. Among-type transitions are inspired by the Tug-of-War process introduced by McFarland et al. (Proc Natl Acad Sci 111(42):15138-15143, 2014) as a mathematical model for competition of advantageous driver mutations and deleterious passenger mutations in cancer cells. We introduce a version of the model in which a driver mutation pushes the type of the cell L-units up, while a passenger mutation pulls it 1-unit down. The distribution of time to divisions depends on the type (fitness) of cell, which is an integer. The extinction probability given any initial cell type is strictly less than 1, which allows us to investigate the transition between types (type transition) in an infinitely long cell lineage of cells. The analysis leads to the result that under driver dominance, the type transition process escapes to infinity, while under passenger dominance, it leads to a limit distribution. Implications in cancer cell dynamics and population genetics are discussed.
    MeSH term(s) Mathematical Concepts ; Models, Biological ; Apoptosis ; Cell Lineage ; Markov Chains ; Neoplasms/genetics
    Language English
    Publishing date 2024-01-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 184905-0
    ISSN 1522-9602 ; 0007-4985 ; 0092-8240
    ISSN (online) 1522-9602
    ISSN 0007-4985 ; 0092-8240
    DOI 10.1007/s11538-023-01245-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book: A systems biology approach to blood

    Corey, Seth J. / Kimmel, Marek / Leonard, Josha N.

    (Advances in experimental medicine and biology ; 844)

    2014  

    Author's details Seth J. Corey ; Marek Kimmel ; Joshua N. Leonard ed
    Series title Advances in experimental medicine and biology ; 844
    Collection
    Keywords Medicine ; Hematology ; Biological models ; Biomedicine
    Language English
    Size IX, 403 S. : Ill., graph. Darst.
    Publisher Springer
    Publishing place New York u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT018534265
    ISBN 978-1-4939-2094-5 ; 9781493920952 ; 1-4939-2094-4 ; 1493920952
    Database Catalogue ZB MED Medicine, Health

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  3. Book ; Online ; E-Book: System engineering approach to planning anticancer therapies

    Świerniak, Andrzej / Kimmel, Marek / Smieja, Jaroslaw / Psiuk-Maksymowicz, Krzysztof / Puszynski, Krzysztof

    2016  

    Author's details Andrzej Świerniak, Marek Kimmel, Jaroslaw Smieja, Krzysztof Psiuk-Maksymowicz, Krzysztof Puszynski
    Keywords population dynamics ; structure models ; biomathematical modelling ; optimimzation ; drug resistance ; cell cycle ; anticancer therapies ; signalling pathway dynamics
    Language English
    Size 1 Online-Ressource (ix, 235 Seiten)
    Publisher Springer
    Publishing place Cham
    Publishing country Germany
    Document type Book ; Online ; E-Book
    Note Lizenzpflichtig
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    HBZ-ID HT019051321
    ISBN 978-3-319-28095-0 ; 9783319280936 ; 3-319-28095-3 ; 3319280937
    DOI 10.1007/978-3-319-28095-0
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  4. Book: Forward time population genetics simulations

    Peng, Bo / Kimmel, Marek / Amos, Christopher I.

    methods, implementation, and applications

    2012  

    Title variant Forward-time population genetics simulations
    Author's details Bo Peng ; Marek Kimmel ; Christopher I. Amos
    Keywords Genetics, Population ; Models, Genetic ; Biological Evolution ; Computer Simulation
    Language English
    Size XXI, 234 S. : Ill., graph. Darst.
    Publisher Wiley-Blackwell
    Publishing place Hoboken, NJ
    Publishing country United States
    Document type Book
    HBZ-ID HT017178358
    ISBN 978-0-470-50348-5 ; 0-470-50348-3
    Database Catalogue ZB MED Medicine, Health

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  5. Article: Modes of Selection in Tumors as Reflected by Two Mathematical Models and Site Frequency Spectra.

    Kurpas, Monika K / Kimmel, Marek

    Frontiers in ecology and evolution

    2022  Volume 10

    Abstract: The tug-of-war model was developed in a series of papers of McFarland and co-authors to account for existence of mutually counteracting rare advantageous driver mutations and more frequent slightly deleterious passenger mutations in cancer. In its ... ...

    Abstract The tug-of-war model was developed in a series of papers of McFarland and co-authors to account for existence of mutually counteracting rare advantageous driver mutations and more frequent slightly deleterious passenger mutations in cancer. In its original version, it was a state-dependent branching process. Because of its formulation, the tug-of-war model is of importance for tackling the problem as to whether evolution of cancerous tumors is "Darwinian" or "non-Darwinian." We define two Time-Continuous Markov Chain versions of the model, including identical mutation processes but adopting different drift and selection components. In Model A, drift and selection process preserves expected fitness whereas in Model B it leads to non-decreasing expected fitness. We investigate these properties using mathematical analysis and extensive simulations, which detect the effect of the so-called drift barrier in Model B but not in Model A. These effects are reflected in different structure of clone genealogies in the two models. Our work is related to the past theoretical work in the field of evolutionary genetics, concerning the interplay among mutation, drift and selection, in absence of recombination (asexual reproduction), where epistasis plays a major role. Finally, we use the statistics of mutation frequencies known as the Site Frequency Spectra (SFS), to compare the variant frequencies in DNA of sequenced HER2+ breast cancers, to those based on Model A and B simulations. The tumor-based SFS are better reproduced by Model A, pointing out a possible selection pattern of HER2+ tumor evolution. To put our models in context, we carried out an exploratory study of how publicly accessible data from breast, prostate, skin and ovarian cancers fit a range of models found in the literature.
    Language English
    Publishing date 2022-08-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2745634-1
    ISSN 2296-701X
    ISSN 2296-701X
    DOI 10.3389/fevo.2022.889438
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Detection and characterization of constitutive replication origins defined by DNA polymerase epsilon.

    Jaksik, Roman / Wheeler, David A / Kimmel, Marek

    BMC biology

    2023  Volume 21, Issue 1, Page(s) 41

    Abstract: Background: Despite the process of DNA replication being mechanistically highly conserved, the location of origins of replication (ORI) may vary from one tissue to the next, or between rounds of replication in eukaryotes, suggesting flexibility in the ... ...

    Abstract Background: Despite the process of DNA replication being mechanistically highly conserved, the location of origins of replication (ORI) may vary from one tissue to the next, or between rounds of replication in eukaryotes, suggesting flexibility in the choice of locations to initiate replication. Lists of human ORI therefore vary widely in number and location, and there are currently no methods available to compare them. Here, we propose a method of detection of ORI based on somatic mutation patterns generated by the mutator phenotype of damaged DNA polymerase epsilon (POLE).
    Results: We report the genome-wide localization of constitutive ORI in POLE-mutated human tumors using whole genome sequencing data. Mutations accumulated after many rounds of replication of unsynchronized dividing cell populations in tumors allow to identify constitutive origins, which we show are shared with high fidelity between individuals and tumor types. Using a Smith-Waterman-like dynamic programming approach, we compared replication origin positions obtained from multiple different methods. The comparison allowed us to define a consensus set of replication origins, identified consistently by multiple ORI detection methods. Many DNA features co-localized with the consensus set of ORI, including chromatin loop anchors, G-quadruplexes, S/MARs, and CpGs. Among all features, the H2A.Z histone exhibited the most significant association.
    Conclusions: Our results show that mutation-based detection of replication origins is a viable approach to determining their location and associated sequence features.
    MeSH term(s) Humans ; DNA Replication ; Replication Origin ; DNA Polymerase II/genetics ; DNA ; Histones/genetics ; Neoplasms/genetics
    Chemical Substances DNA Polymerase II (EC 2.7.7.7) ; DNA (9007-49-2) ; Histones
    Language English
    Publishing date 2023-02-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2133020-7
    ISSN 1741-7007 ; 1741-7007
    ISSN (online) 1741-7007
    ISSN 1741-7007
    DOI 10.1186/s12915-023-01527-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book ; Online: A Countable-Type Branching Process Model for the Tug-of-War Cancer Cell Dynamics

    Wang, Ren-Yi / Kimmel, Marek

    2023  

    Abstract: We consider a time-continuous Markov branching process of proliferating cells with a countable collection of types. Among-type transitions are inspired by the Tug-of-War process introduced in McFarland et al. as a mathematical model for competition of ... ...

    Abstract We consider a time-continuous Markov branching process of proliferating cells with a countable collection of types. Among-type transitions are inspired by the Tug-of-War process introduced in McFarland et al. as a mathematical model for competition of advantageous driver mutations and deleterious passenger mutations in cancer cells. We introduce a version of the model in which a driver mutation pushes the type of the cell $L$-units up, while a passenger mutation pulls it $1$-unit down. The distribution of time to divisions depends on the type (fitness) of cell, which is an integer. The extinction probability given any initial cell type is strictly less than $1$, which allows us to investigate the transition between types (type transition) in an infinitely long cell lineage of cells. The analysis leads to the result that under driver dominance, the type transition process escapes to infinity, while under passenger dominance, it leads to a limit distribution. Implications in cancer cell dynamics and population genetics are discussed.
    Keywords Quantitative Biology - Populations and Evolution ; Mathematics - Probability
    Subject code 519 ; 612
    Publishing date 2023-02-16
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Correction: Kurpas et al. Genomic Analysis of SARS-CoV-2 Alpha, Beta and Delta Variants of Concern Uncovers Signatures of Neutral and Non-Neutral Evolution.

    Kurpas, Monika Klara / Jaksik, Roman / Kuś, Pawel / Kimmel, Marek

    Viruses

    2023  Volume 15, Issue 5

    Abstract: ... Missing ... ...

    Abstract Missing Funding
    Language English
    Publishing date 2023-04-25
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15051047
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Book ; Online: Stochastic Models of Stem Cells and Their Descendants under Different Criticality Assumptions

    Nguyen, Nam H / Kimmel, Marek

    2022  

    Abstract: We study time continuous branching processes with exponentially distributed lifetimes, with two types of cells that proliferate according to binary fission. A range of possible system dynamics are considered, each of which is characterized by the ... ...

    Abstract We study time continuous branching processes with exponentially distributed lifetimes, with two types of cells that proliferate according to binary fission. A range of possible system dynamics are considered, each of which is characterized by the mutation rate of the original cells and the survival probability of the altered cells' progeny. For each system, we derive a closed-form expression for the joint probability generating function of cell counts, and perform asymptotic analysis on the behaviors of the cell population with particular focus on probability of extinction. Part of our results confirms known properties of branching processes using a different approach while other are original. While the model is best suited for modeling the fate of differentiating stem cells, we discuss other scenarios in which these system dynamics may be applicable in real life. We also discuss the history of the subject.

    Comment: 23 pages including abstract, references, and supplement
    Keywords Mathematics - Probability ; Mathematics - Statistics Theory ; Statistics - Computation
    Subject code 612
    Publishing date 2022-04-25
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Mutation patterns in SARS-COV-2 Alpha and Beta variants indicate non-neutral evolution

    Kurpas, Monika Klara / Kimmel, Marek

    bioRxiv

    Abstract: Due to the emergence of new variants of the SARS-CoV-2 coronavirus, the question of how the viral genomes evolved, leading to the formation of highly infectious strains, becomes particularly important. Two early emergent strains, Alpha and Beta, ... ...

    Abstract Due to the emergence of new variants of the SARS-CoV-2 coronavirus, the question of how the viral genomes evolved, leading to the formation of highly infectious strains, becomes particularly important. Two early emergent strains, Alpha and Beta, characterized by a significant number of missense mutations, provide natural testing samples. In this study we are exploring the history of each of the segregating sites present in Alpha and Beta variants of concern, to address the question whether defining mutations were accumulating gradually leading to the formation of sequence characteristic of these variants. Our analysis exposes data features that suggest other than neutral evolution of SARS-CoV-2 genomes, leading to emergence of variants of concern. We observe only small number of possible combinations of mutations indicating rapid evolution of genomes. In addtion, mutation patterns observed in whole genome samples of Alpha and Beta variants also indicate presence of stronger selection than in remaining genome samples.
    Keywords covid19
    Language English
    Publishing date 2022-03-01
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.02.28.482283
    Database COVID19

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