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  1. Book: Targeted cancer treatment in silico

    Komarova, Natalia L. / Wodarz, Dominik

    small molecule inhibitors and oncolytic viruses

    (Modeling and simulation in science, engineering and technology)

    2014  

    Author's details Natalia L. Komarova ; Dominik Wodarz
    Series title Modeling and simulation in science, engineering and technology
    Language English
    Size XV, 327 S. : Ill., graph. Darst.
    Publisher Birkhäuser
    Publishing place New York
    Publishing country United States
    Document type Book
    HBZ-ID HT018105740
    ISBN 978-1-4614-8300-7 ; 9781461483014 ; 1-4614-8300-X ; 1461483018
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    2013 A 4173 available for loan (reading room) Lesesaal EG

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  2. Article ; Online: Mutant fixation in the presence of a natural enemy.

    Wodarz, Dominik / Komarova, Natalia L

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 6642

    Abstract: The literature about mutant invasion and fixation typically assumes populations to exist in isolation from their ecosystem. Yet, populations are part of ecological communities, and enemy-victim (e.g. predator-prey or pathogen-host) interactions are ... ...

    Abstract The literature about mutant invasion and fixation typically assumes populations to exist in isolation from their ecosystem. Yet, populations are part of ecological communities, and enemy-victim (e.g. predator-prey or pathogen-host) interactions are particularly common. We use spatially explicit, computational pathogen-host models (with wild-type and mutant hosts) to re-visit the established theory about mutant fixation, where the pathogen equally attacks both wild-type and mutant individuals. Mutant fitness is assumed to be unrelated to infection. We find that pathogen presence substantially weakens selection, increasing the fixation probability of disadvantageous mutants and decreasing it for advantageous mutants. The magnitude of the effect rises with the infection rate. This occurs because infection induces spatial structures, where mutant and wild-type individuals are mostly spatially separated. Thus, instead of mutant and wild-type individuals competing with each other, it is mutant and wild-type "patches" that compete, resulting in smaller fitness differences and weakened selection. This implies that the deleterious mutant burden in natural populations might be higher than expected from traditional theory.
    MeSH term(s) Humans ; Models, Biological ; Ecosystem ; Probability ; Population Dynamics
    Language English
    Publishing date 2023-10-20
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-41787-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Multi-scale network targeting: A holistic systems-biology approach to cancer treatment.

    Paul, Doru / Komarova, Natalia L

    Progress in biophysics and molecular biology

    2021  Volume 165, Page(s) 72–79

    Abstract: The vulnerabilities of cancer at the cellular and, recently, with the introduction of immunotherapy, at the tissue level, have been exploited with variable success. Evaluating the cancer system vulnerabilities at the organismic level through analysis of ... ...

    Abstract The vulnerabilities of cancer at the cellular and, recently, with the introduction of immunotherapy, at the tissue level, have been exploited with variable success. Evaluating the cancer system vulnerabilities at the organismic level through analysis of network topology and network dynamics can potentially predict novel anti-cancer drug targets directed at the macroscopic cancer networks. Theoretical work analyzing the properties and the vulnerabilities of the multi-scale network of cancer needs to go hand-in-hand with experimental research that uncovers the biological nature of the relevant networks and reveals new targetable vulnerabilities. It is our hope that attacking cancer on different spatial scales, in a concerted integrated approach, may present opportunities for novel ways to prevent treatment resistance.
    MeSH term(s) Humans ; Neoplasms/drug therapy ; Systems Biology
    Language English
    Publishing date 2021-08-21
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209302-9
    ISSN 1873-1732 ; 0079-6107
    ISSN (online) 1873-1732
    ISSN 0079-6107
    DOI 10.1016/j.pbiomolbio.2021.08.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.281: Show issues Location:
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  4. Book: Computational biology of cancer

    Wodarz, Dominik / Komarova, Natalia L.

    lecture notes and mathematical modeling

    2005  

    Author's details Dominik Wodarz ; Natalia L. Komarova
    Keywords Cancer/Mathematical models
    Subject code 616.994
    Language English
    Size XIV, 250 S. : graph. Darst.
    Publisher World Scientific
    Publishing place Singapore
    Publishing country Singapore
    Document type Book
    HBZ-ID HT014554804
    ISBN 981-256-027-0 ; 978-981-256-027-8
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    2006 A 3554 order for loan Magazin

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  5. Article ; Online: Nicotiana benthamiana

    Kamarova, Kamila A / Ershova, Natalia M / Sheshukova, Ekaterina V / Arifulin, Eugene A / Ovsiannikova, Natalia L / Antimonova, Alexandra A / Kudriashov, Andrei A / Komarova, Tatiana V

    International journal of molecular sciences

    2023  Volume 24, Issue 16

    Abstract: Reversibly glycosylated polypeptides (RGPs) have been identified in many plant species and play an important role in cell wall formation, intercellular transport regulation, and plant-virus interactions. Most plants have ... ...

    Abstract Reversibly glycosylated polypeptides (RGPs) have been identified in many plant species and play an important role in cell wall formation, intercellular transport regulation, and plant-virus interactions. Most plants have several
    MeSH term(s) Nicotiana/genetics ; Tobacco Mosaic Virus ; Peptides ; Glycosylation ; Antiviral Agents
    Chemical Substances Peptides ; Antiviral Agents
    Language English
    Publishing date 2023-08-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241612843
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Mutant Evolution in Spatially Structured and Fragmented Expanding Populations.

    Wodarz, Dominik / Komarova, Natalia L

    Genetics

    2020  Volume 216, Issue 1, Page(s) 191–203

    Abstract: Mutant evolution in spatially structured systems is important for a range of biological systems, but aspects of it still require further elucidation. Adding to previous work, we provide a simple derivation of growth laws that characterize the number of ... ...

    Abstract Mutant evolution in spatially structured systems is important for a range of biological systems, but aspects of it still require further elucidation. Adding to previous work, we provide a simple derivation of growth laws that characterize the number of mutants of different relative fitness in expanding populations in spatial models of different dimensionalities. These laws are universal and independent of "microscopic" modeling details. We further study the accumulation of mutants and find that, with advantageous and neutral mutants, more of them are present in spatially structured, compared to well-mixed colonies of the same size. The behavior of disadvantageous mutants is subtle: if they are disadvantageous through a reduction in division rates, the result is the same, and it is the opposite if the disadvantage is due to a death rate increase. Finally, we show that in all cases, the same results are observed in fragmented, nonspatial patch models. This suggests that the patterns observed are the consequence of population fragmentation, and not spatial restrictions
    MeSH term(s) Bacteria/genetics ; Evolution, Molecular ; Genetic Fitness ; Models, Genetic ; Mutation
    Language English
    Publishing date 2020-07-13
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2167-2
    ISSN 1943-2631 ; 0016-6731
    ISSN (online) 1943-2631
    ISSN 0016-6731
    DOI 10.1534/genetics.120.303422
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 767: 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)

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  7. Article ; Online: Cancer: A moving target.

    Komarova, Natalia L

    Nature

    2015  Volume 525, Issue 7568, Page(s) 198–199

    MeSH term(s) Cell Movement ; Genetic Variation/genetics ; Humans ; Models, Biological ; Neoplasms/genetics ; Neoplasms/pathology ; Selection, Genetic
    Language English
    Publishing date 2015-09-10
    Publishing country England
    Document type Comment ; Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/nature15210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 26: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 9: Show issues
    Zs.MO 244: Show issues

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  8. Article ; Online: The benefits of treating undetectable tumors.

    Komarova, Natalia L

    eLife

    2015  Volume 4, Page(s) e09713

    Abstract: Cancer prevention is predicted to result in more positive therapeutic outcomes than post-diagnostic interventions, and so may be a viable option for future personalized medicine. ...

    Abstract Cancer prevention is predicted to result in more positive therapeutic outcomes than post-diagnostic interventions, and so may be a viable option for future personalized medicine.
    MeSH term(s) Humans ; Models, Theoretical ; Neoplasms/prevention & control ; Neoplasms/therapy
    Language English
    Publishing date 2015-08-05
    Publishing country England
    Document type Comment ; Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.09713
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  9. Article ; Online: Effect of Human Behavior on the Evolution of Viral Strains During an Epidemic.

    Azizi, Asma / Kazanci, Caner / Komarova, Natalia L / Wodarz, Dominik

    Bulletin of mathematical biology

    2022  Volume 84, Issue 12, Page(s) 144

    Abstract: It is well known in the literature that human behavior can change as a reaction to disease observed in others, and that such behavioral changes can be an important factor in the spread of an epidemic. It has been noted that human behavioral traits in ... ...

    Abstract It is well known in the literature that human behavior can change as a reaction to disease observed in others, and that such behavioral changes can be an important factor in the spread of an epidemic. It has been noted that human behavioral traits in disease avoidance are under selection in the presence of infectious diseases. Here, we explore a complementary trend: the pathogen itself might experience a force of selection to become less "visible," or less "symptomatic," in the presence of such human behavioral trends. Using a stochastic SIR agent-based model, we investigated the co-evolution of two viral strains with cross-immunity, where the resident strain is symptomatic while the mutant strain is asymptomatic. We assumed that individuals exercised self-regulated social distancing (SD) behavior if one of their neighbors was infected with a symptomatic strain. We observed that the proportion of asymptomatic carriers increased over time with a stronger effect corresponding to higher levels of self-regulated SD. Adding mandated SD made the effect more significant, while the existence of a time-delay between the onset of infection and the change of behavior reduced the advantage of the asymptomatic strain. These results were consistent under random geometric networks, scale-free networks, and a synthetic network that represented the social behavior of the residents of New Orleans.
    MeSH term(s) Humans ; Models, Biological ; Mathematical Concepts ; Epidemics
    Language English
    Publishing date 2022-11-05
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; 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/s11538-022-01102-7
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    In stock of ZB MED Cologne/Königswinter

    Zs.B 754: Show issues Location:
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  10. Article ; Online: A hybrid stochastic-deterministic approach to explore multiple infection and evolution in HIV.

    Kreger, Jesse / Komarova, Natalia L / Wodarz, Dominik

    PLoS computational biology

    2021  Volume 17, Issue 12, Page(s) e1009713

    Abstract: To study viral evolutionary processes within patients, mathematical models have been instrumental. Yet, the need for stochastic simulations of minority mutant dynamics can pose computational challenges, especially in heterogeneous systems where very ... ...

    Abstract To study viral evolutionary processes within patients, mathematical models have been instrumental. Yet, the need for stochastic simulations of minority mutant dynamics can pose computational challenges, especially in heterogeneous systems where very large and very small sub-populations coexist. Here, we describe a hybrid stochastic-deterministic algorithm to simulate mutant evolution in large viral populations, such as acute HIV-1 infection, and further include the multiple infection of cells. We demonstrate that the hybrid method can approximate the fully stochastic dynamics with sufficient accuracy at a fraction of the computational time, and quantify evolutionary end points that cannot be expressed by deterministic models, such as the mutant distribution or the probability of mutant existence at a given infected cell population size. We apply this method to study the role of multiple infection and intracellular interactions among different virus strains (such as complementation and interference) for mutant evolution. Multiple infection is predicted to increase the number of mutants at a given infected cell population size, due to a larger number of infection events. We further find that viral complementation can significantly enhance the spread of disadvantageous mutants, but only in select circumstances: it requires the occurrence of direct cell-to-cell transmission through virological synapses, as well as a substantial fitness disadvantage of the mutant, most likely corresponding to defective virus particles. This, however, likely has strong biological consequences because defective viruses can carry genetic diversity that can be incorporated into functional virus genomes via recombination. Through this mechanism, synaptic transmission in HIV might promote virus evolvability.
    MeSH term(s) Algorithms ; Cells/virology ; Computational Biology ; Evolution, Molecular ; HIV Infections/genetics ; HIV Infections/transmission ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/pathogenicity ; Host-Pathogen Interactions/genetics ; Humans ; Mutation/genetics ; Stochastic Processes ; Virus Replication/genetics
    Language English
    Publishing date 2021-12-22
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1009713
    Database MEDical Literature Analysis and Retrieval System OnLINE

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