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1دورية أكاديمية
المؤلفون: Yosef E Maruvka, Min Tang, Franziska Michor
المصدر: PLoS ONE, Vol 9, Iss 7, p e83100 (2014)
الوصف: The 5-year survival rate of cancer patients is the most commonly used statistic to reflect improvements in the war against cancer. This idea, however, was refuted based on an analysis showing that changes in 5-year survival over time bear no relationship with changes in cancer mortality.Here we show that progress in the fight against cancer can be evaluated by analyzing the association between 5-year survival rates and mortality rates normalized by the incidence (mortality over incidence, MOI). Changes in mortality rates are caused by improved clinical management as well as changing incidence rates, and since the latter can mask the effects of the former, it can also mask the correlation between survival and mortality rates. However, MOI is a more robust quantity and reflects improvements in cancer outcomes by overcoming the masking effect of changing incidence rates. Using population-based statistics for the US and the European Nordic countries, we determined the association of changes in 5-year survival rates and MOI.We observed a strong correlation between changes in 5-year survival rates of cancer patients and changes in the MOI for all the countries tested. This finding demonstrates that there is no reason to assume that the improvements in 5-year survival rates are artificial. We obtained consistent results when examining the subset of cancer types whose incidence did not increase, suggesting that over-diagnosis does not obscure the results.We have demonstrated, via the negative correlation between changes in 5-year survival rates and changes in MOI, that increases in 5-year survival rates reflect real improvements over time made in the clinical management of cancer. Furthermore, we found that increases in 5-year survival rates are not predominantly artificial byproducts of lead-time bias, as implied in the literature. The survival measure alone can therefore be used for a rough approximation of the amount of progress in the clinical management of cancer, but should ideally be used with other measures.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC4108307?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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2دورية أكاديمية
المؤلفون: Noa Chapal-Ilani, Yosef E Maruvka, Adam Spiro, Yitzhak Reizel, Rivka Adar, Liran I Shlush, Ehud Shapiro
المصدر: PLoS Computational Biology, Vol 9, Iss 11, p e1003297 (2013)
مصطلحات موضوعية: Biology (General), QH301-705.5
الوصف: Organism cells proliferate and die to build, maintain, renew and repair it. The cellular history of an organism up to any point in time can be captured by a cell lineage tree in which vertices represent all organism cells, past and present, and directed edges represent progeny relations among them. The root represents the fertilized egg, and the leaves represent extant and dead cells. Somatic mutations accumulated during cell division endow each organism cell with a genomic signature that is unique with a very high probability. Distances between such genomic signatures can be used to reconstruct an organism's cell lineage tree. Cell populations possess unique features that are absent or rare in organism populations (e.g., the presence of stem cells and a small number of generations since the zygote) and do not undergo sexual reproduction, hence the reconstruction of cell lineage trees calls for careful examination and adaptation of the standard tools of population genetics. Our lab developed a method for reconstructing cell lineage trees by examining only mutations in highly variable microsatellite loci (MS, also called short tandem repeats, STR). In this study we use experimental data on somatic mutations in MS of individual cells in human and mice in order to validate and quantify the utility of known lineage tree reconstruction algorithms in this context. We employed extensive measurements of somatic mutations in individual cells which were isolated from healthy and diseased tissues of mice and humans. The validation was done by analyzing the ability to infer known and clear biological scenarios. In general, we found that if the biological scenario is simple, almost all algorithms tested can infer it. Another somewhat surprising conclusion is that the best algorithm among those tested is Neighbor Joining where the distance measure used is normalized absolute distance. We include our full dataset in Tables S1, S2, S3, S4, S5 to enable further analysis of this data by others.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC3828138?pdf=renderTest; https://doaj.org/toc/1553-734XTest; https://doaj.org/toc/1553-7358Test
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3دورية أكاديمية
المؤلفون: Hiroshi Haeno, Yosef E Maruvka, Yoh Iwasa, Franziska Michor
المصدر: PLoS ONE, Vol 8, Iss 6, p e65724 (2013)
الوصف: Cancer initiation, progression, and the emergence of drug resistance are driven by specific genetic and/or epigenetic alterations such as point mutations, structural alterations, DNA methylation and histone modification changes. These alterations may confer advantageous, deleterious or neutral effects to mutated cells. Previous studies showed that cells harboring two particular alterations may arise in a fixed-size population even in the absence of an intermediate state in which cells harboring only the first alteration take over the population; this phenomenon is called stochastic tunneling. Here, we investigated a stochastic Moran model in which two alterations emerge in a cell population of fixed size. We developed a novel approach to comprehensively describe the evolutionary dynamics of stochastic tunneling of two mutations. We considered the scenarios of large mutation rates and various fitness values and validated the accuracy of the mathematical predictions with exact stochastic computer simulations. Our theory is applicable to situations in which two alterations are accumulated in a fixed-size population of binary dividing cells.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC3694076?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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4دورية أكاديمية
المؤلفون: Yitzhak Reizel, Shalev Itzkovitz, Rivka Adar, Judith Elbaz, Adrian Jinich, Noa Chapal-Ilani, Yosef E Maruvka, Nava Nevo, Zipora Marx, Inna Horovitz, Adam Wasserstrom, Avi Mayo, Irena Shur, Dafna Benayahu, Karl Skorecki, Eran Segal, Nava Dekel, Ehud Shapiro
المصدر: PLoS Genetics, Vol 8, Iss 2, p e1002477 (2012)
الوصف: Fundamental aspects of embryonic and post-natal development, including maintenance of the mammalian female germline, are largely unknown. Here we employ a retrospective, phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites, to study female germline dynamics in mice. Reconstructed cell lineage trees can be used to estimate lineage relationships between different cell types, as well as cell depth (number of cell divisions since the zygote). We show that, in the reconstructed mouse cell lineage trees, oocytes form clusters that are separate from hematopoietic and mesenchymal stem cells, both in young and old mice, indicating that these populations belong to distinct lineages. Furthermore, while cumulus cells sampled from different ovarian follicles are distinctly clustered on the reconstructed trees, oocytes from the left and right ovaries are not, suggesting a mixing of their progenitor pools. We also observed an increase in oocyte depth with mouse age, which can be explained either by depth-guided selection of oocytes for ovulation or by post-natal renewal. Overall, our study sheds light on substantial novel aspects of female germline preservation and development.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC3285577?pdf=renderTest; https://doaj.org/toc/1553-7390Test; https://doaj.org/toc/1553-7404Test
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5دورية أكاديمية
المؤلفون: Yitzhak Reizel, Noa Chapal-Ilani, Rivka Adar, Shalev Itzkovitz, Judith Elbaz, Yosef E Maruvka, Elad Segev, Liran I Shlush, Nava Dekel, Ehud Shapiro
المصدر: PLoS Genetics, Vol 7, Iss 7, p e1002192 (2011)
الوصف: Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC3145618?pdf=renderTest; https://doaj.org/toc/1553-7390Test; https://doaj.org/toc/1553-7404Test
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6دورية أكاديمية
المؤلفون: Yosef E Maruvka, David A Kessler, Nadav M Shnerb
المصدر: PLoS ONE, Vol 6, Iss 11, p e26480 (2011)
الوصف: Fat tailed statistics and power-laws are ubiquitous in many complex systems. Usually the appearance of of a few anomalously successful individuals (bio-species, investors, websites) is interpreted as reflecting some inherent "quality" (fitness, talent, giftedness) as in Darwin's theory of natural selection. Here we adopt the opposite, "neutral", outlook, suggesting that the main factor explaining success is merely luck. The statistics emerging from the neutral birth-death-mutation (BDM) process is shown to fit marvelously many empirical distributions. While previous neutral theories have focused on the power-law tail, our theory economically and accurately explains the entire distribution. We thus suggest the BDM distribution as a standard neutral model: effects of fitness and selection are to be identified by substantial deviations from it.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC3206027?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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7دورية أكاديمية
المؤلفون: Yosef E Maruvka, Nadav M Shnerb
المصدر: PLoS Computational Biology, Vol 5, Iss 4, p e1000359 (2009)
مصطلحات موضوعية: Biology (General), QH301-705.5
الوصف: What is the underlying mechanism behind the fat-tailed statistics observed for species abundance distributions? The two main hypotheses in the field are the adaptive (niche) theories, where species abundance reflects its fitness, and the neutral theory that assumes demographic stochasticity as the main factor determining community structure. Both explanations suggest quite similar species-abundance distributions, but very different histories: niche scenarios assume that a species population in the past was similar to the observed one, while neutral scenarios are characterized by strongly fluctuating populations. Since the genetic variations within a population depend on its abundance in the past, we present here a way to discriminate between the theories using the genetic diversity of noncoding DNA. A statistical test, based on the Fu-Li method, has been developed and enables such a differentiation. We have analyzed the results gathered from individual-based simulation of both types of histories and obtained clear distinction between the Fu-Li statistics of the neutral scenario and that of the niche scenario. Our results suggest that data for 10-50 species, with approximately 30 sequenced individuals for each species, may allow one to distinguish between these two theories.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC2667257?pdf=renderTest; https://doaj.org/toc/1553-734XTest; https://doaj.org/toc/1553-7358Test
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8دورية أكاديمية
المؤلفون: Anirban Das, Nicholas R. Fernandez, Adrian Levine, Vanessa Bianchi, Lucie K. Stengs, Jiil Chung, Logine Negm, Jose Rafael Dimayacyac, Yuan Chang, Liana Nobre, Ayse B. Ercan, Santiago Sanchez-Ramirez, Sumedha Sudhaman, Melissa Edwards, Valerie Larouche, David Samuel, An Van Damme, David Gass, David S. Ziegler, Stefan S. Bielack, Carl Koschmann, Shayna Zelcer, Michal Yalon-Oren, Gadi Abede Campino, Tomasz Sarosiek, Kim E. Nichols, Rebecca Loret De Mola, Kevin Bielamowicz, Magnus Sabel, Charlotta A. Frojd, Matthew D. Wood, Jason M. Glover, Yi-Yen Lee, Magimairajan Vanan, Jenny K. Adamski, Sebastien Perreault, Omar Chamdine, Magnus Aasved Hjort, Michal Zapotocky, Fernando Carceller, Erin Wright, Ivana Fedorakova, Alexander Lossos, Ryuma Tanaka, Michael Osborn, Deborah T. Blumenthal, Melyssa Aronson, Ute Bartels, Annie Huang, Vijay Ramaswamy, David Malkin, Adam Shlien, Anita Villani, Peter B. Dirks, Trevor J. Pugh, Gad Getz, Yosef E. Maruvka, Derek S. Tsang, Birgit Ertl-Wagner, Cynthia Hawkins, Eric Bouffet, Daniel A. Morgenstern, Uri Tabori
مصطلحات موضوعية: Cancer, Tumor Biology, Cancer Detection and Diagnosis, Therapeutic Research and Development, Immuno-oncology, Clinical Research and Trials, Biomarkers, Clinical-stage Research, CNS Cancers, Gliomas, Glioblastomas, Immunotherapy, Checkpoint blockade, Pediatric Cancers, Translational Research, Tumor Evolution, Tumor Microenvironment
الوصف: Supplementary Figures S1 to S5, with each figure followed by its corresponding legend in the next page
الإتاحة: https://doi.org/10.1158/2159-8290.25183895.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_Figures_S1-S5_from_Combined_Immunotherapy_Improves_Outcome_for_Replication-Repair-Deficient_RRD_High-Grade_Glioma_Failing_Anti_PD-1_Monotherapy_A_Report_from_the_International_RRD_Consortium/25183895Test -
9دورية أكاديمية
المؤلفون: Anirban Das, Nicholas R. Fernandez, Adrian Levine, Vanessa Bianchi, Lucie K. Stengs, Jiil Chung, Logine Negm, Jose Rafael Dimayacyac, Yuan Chang, Liana Nobre, Ayse B. Ercan, Santiago Sanchez-Ramirez, Sumedha Sudhaman, Melissa Edwards, Valerie Larouche, David Samuel, An Van Damme, David Gass, David S. Ziegler, Stefan S. Bielack, Carl Koschmann, Shayna Zelcer, Michal Yalon-Oren, Gadi Abede Campino, Tomasz Sarosiek, Kim E. Nichols, Rebecca Loret De Mola, Kevin Bielamowicz, Magnus Sabel, Charlotta A. Frojd, Matthew D. Wood, Jason M. Glover, Yi-Yen Lee, Magimairajan Vanan, Jenny K. Adamski, Sebastien Perreault, Omar Chamdine, Magnus Aasved Hjort, Michal Zapotocky, Fernando Carceller, Erin Wright, Ivana Fedorakova, Alexander Lossos, Ryuma Tanaka, Michael Osborn, Deborah T. Blumenthal, Melyssa Aronson, Ute Bartels, Annie Huang, Vijay Ramaswamy, David Malkin, Adam Shlien, Anita Villani, Peter B. Dirks, Trevor J. Pugh, Gad Getz, Yosef E. Maruvka, Derek S. Tsang, Birgit Ertl-Wagner, Cynthia Hawkins, Eric Bouffet, Daniel A. Morgenstern, Uri Tabori
مصطلحات موضوعية: Cancer, Tumor Biology, Cancer Detection and Diagnosis, Therapeutic Research and Development, Immuno-oncology, Clinical Research and Trials, Biomarkers, Clinical-stage Research, CNS Cancers, Gliomas, Glioblastomas, Immunotherapy, Checkpoint blockade, Pediatric Cancers, Translational Research, Tumor Evolution, Tumor Microenvironment
الوصف: Demographics and details of treatment in patients who continued ICI progression (n=38)
الإتاحة: https://doi.org/10.1158/2159-8290.25183886.v1Test
https://figshare.com/articles/journal_contribution/Table_S2_from_Combined_Immunotherapy_Improves_Outcome_for_Replication-Repair-Deficient_RRD_High-Grade_Glioma_Failing_Anti_PD-1_Monotherapy_A_Report_from_the_International_RRD_Consortium/25183886Test -
10دورية أكاديمية
المؤلفون: Anirban Das, Uri Tabori, Lauren C. Sambira Nahum, Natalie B. Collins, Rebecca Deyell, Rina Dvir, Cecile Faure-Conter, Timothy E. Hassall, Jane E. Minturn, Melissa Edwards, Elissa Brookes, Vanessa Bianchi, Adrian Levine, Simone C. Stone, Sumedha Sudhaman, Santiago Sanchez Ramirez, Ayse B. Ercan, Lucie Stengs, Jill Chung, Logine Negm, Gad Getz, Yosef E. Maruvka, Birgit Ertl-Wagner, Pamela S. Ohashi, Trevor Pugh, Cynthia Hawkins, Eric Bouffet, Daniel A. Morgenstern
مصطلحات موضوعية: Cancer
الوصف: Full trial protocol NCT02992964
الإتاحة: https://doi.org/10.1158/1078-0432.24710470.v1Test
https://figshare.com/articles/journal_contribution/Trial_protocol_1_from_Efficacy_of_Nivolumab_in_Pediatric_Cancers_with_High_Mutation_Burden_and_Mismatch_Repair_Deficiency/24710470Test
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