Article
Multidisciplinary Sciences
Markus Pfenninger, Halina Binde Doria, Jana Nickel, Anne Thielsch, Klaus Schwenk, Mathilde Cordellier
Summary: Mutations serve as the driving force for evolution, but the direct estimation of mutation rates is limited to a few species. This study estimated the spontaneous single nucleotide mutation rate in the waterflea Daphnia galeata using a mutation accumulation approach. The findings show a slightly lower mutation rate compared to other Daphnia species.
Article
Biochemical Research Methods
Simone Ciccolella, Camir Ricketts, Mauricio Soto Gomez, Murray Patterson, Dana Silverbush, Paola Bonizzoni, Iman Hajirasouliha, Gianluca Della Vedova
Summary: Recent studies have identified limitations in current computational methods for inferring tumor phylogenies. The new SASC approach, based on simulated annealing and using the Dollo-k model, demonstrates high accuracy in inferring cancer progressions.
Article
Multidisciplinary Sciences
Benjamin J. Hershey, Sara Barozzi, Fabrizio Orsenigo, Simone Pompei, Fabio Iannelli, Stephan Kamrad, Vittoria Matafora, Federica Pisati, Ludovico Calabrese, Giuseppe Fragale, Giulia Salvadori, Emanuele Martini, Maria Grazia Totaro, Serena Magni, Rui Guan, Dario Parazzoli, Paolo Maiuri, Angela Bachi, Kiran R. Patil, Marco Cosentino Lagomarsino, Kristina M. Havas
Summary: Tumors exhibit significant genetic and phenotypic diversity. Ecological interactions between tumor cell lineages can sustain diversity and promote metastasis. It has been discovered that cooperative ecological interactions between tumor cell lineages can alleviate growth barriers and enhance metastasis.
Article
Cell Biology
Thomas Veith, Andrew Schultz, Saeed Alahmari, Richard Beck, Joseph Johnson, Noemi Andor
Summary: Many cancer cell lines are aneuploid and heterogeneous, with multiple karyotypes co-existing. Karyotype heterogeneity affects cellular phenotypes and drug response. In this study, single cell sequencing data was analyzed to understand the phenotypic implications of karyotype heterogeneity. Differences in growth rate and contact inhibition were quantified and used to identify biomarkers, revealing significant variations in predicted growth rate or carrying capacity among different karyotypes. Models based on these predictions can be useful in designing density-dependent selection experiments.
Article
Biochemistry & Molecular Biology
Aurelie Mesnil, Maude Jacquot, Celine Garcia, Delphine Tourbiez, Lydie Canier, Audrey Bidois, Lionel Degremont, Deborah Cheslett, Michelle Geary, Alessia Vetri, Ana Roque, Dolors Furones, Alison Garden, Petya Orozova, Isabelle Arzul, Mathieu Sicard, Guillaume M. Charriere, Delphine Destoumieux-Garzon, Marie-Agnes Travers
Summary: This article investigates the evolutionary mechanisms of Vibrio aestuarianus, a pathogen causing oyster mortality in France and Ireland, and reveals its classical epidemic population structure. The acquisition of a copper-containing island may have facilitated the emergence of pathogenic lineages specialized in oysters.
Article
Biochemistry & Molecular Biology
Katrina B. Harris, Kenneth M. Flynn, Vaughn S. Cooper
Summary: Evolution and diversification of Pseudomonas aeruginosa populations in biofilm-promoting environments show that adaptation and genetic variation are maintained without the usual elimination of diversity by fixation events. Multiple mutations are preserved at intermediate frequencies, suggesting that some environments may expose a larger fraction of the genome and select for many adaptations at once. This challenges the conventional idea that strong selection would normally purge genetic and phenotypic diversity.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biochemical Research Methods
Jack Kuipers, Jochen Singer, Niko Beerenwinkel
Summary: This study presents a method to jointly call mutations in each cell, reconstruct the phylogenetic relationship between cells, and determine the locations of mutational losses and recurrences by modelling the noise processes and allowing mutations to be lost or to reoccur during tumour evolution. The method allows the resolution of tumour heterogeneity and accurate calling of mutations.
Review
Pharmacology & Pharmacy
Martyna Jaworska, Julia Szczudlo, Adrian Pietrzyk, Jay Shah, Sonia E. Trojan, Barbara Ostrowska, Kinga A. Kocemba-Pilarczyk
Summary: Although Warburg's discovery of intensive glucose uptake and lactate fermentation in tumors is a century old, it remains an area of active research. This metabolic reprogramming of cancer cells has implications for various processes such as cell signaling, proliferation, energy supply, and immunosuppression. The Warburg effect is regulated by signaling pathways like PI3K/Akt/mTOR and transcription factors like HIF-1, p53, and c-Myc, and it plays a role in meeting the metabolic demands of rapidly proliferating tumor cells. Lactate, the end-product of aerobic glycolysis, acts as an oncometabolite that can provide fuel for neighboring cancer cells and promote metastasis and immunosuppression.
PHARMACOLOGICAL REPORTS
(2023)
Article
Biotechnology & Applied Microbiology
Li Tai Fang, Bin Zhu, Yongmei Zhao, Wanqiu Chen, Zhaowei Yang, Liz Kerrigan, Kurt Langenbach, Maryellen de Mars, Charles Lu, Kenneth Idler, Howard Jacob, Yuanting Zheng, Luyao Ren, Ying Yu, Erich Jaeger, Gary P. Schroth, Ogan D. Abaan, Keyur Talsania, Justin Lack, Tsai-Wei Shen, Zhong Chen, Seta Stanbouly, Bao Tran, Jyoti Shetty, Yuliya Kriga, Daoud Meerzaman, Cu Nguyen, Virginie Petitjean, Marc Sultan, Margaret Cam, Monika Mehta, Tiffany Hung, Eric Peters, Rasika Kalamegham, Sayed Mohammad Ebrahim Sahraeian, Marghoob Mohiyuddin, Yunfei Guo, Lijing Yao, Lei Song, Hugo Y. K. Lam, Jiri Drabek, Petr Vojta, Roberta Maestro, Daniela Gasparotto, Sulev Koks, Ene Reimann, Andreas Scherer, Jessica Nordlund, Ulrika Liljedahl, Roderick Jensen, Mehdi Pirooznia, Zhipan Li, Chunlin Xiao, Stephen T. Sherry, Rebecca Kusko, Malcolm Moos, Eric Donaldson, Zivana Tezak, Baitang Ning, Weida Tong, Jing Li, Penelope Duerken-Hughes, Claudia Catalanotti, Shamoni Maheshwari, Joe Shuga, Winnie S. Liang, Jonathan Keats, Jonathan Adkins, Erica Tassone, Victoria Zismann, Timothy McDaniel, Jeffrey Trent, Jonathan Foox, Daniel Butler, Christopher E. Mason, Huixiao Hong, Leming Shi, Charles Wang, Wenming Xiao
Summary: This study presents reference call sets obtained from paired tumor-normal genomic DNA samples from a breast cancer cell line and a lymphoblastoid cell line. These samples were partially validated for somatic mutations and germline variants through whole-exome sequencing and targeted sequencing. The use of these samples can help calibrate clinical sequencing pipelines and provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.
NATURE BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Sohrab Salehi, Farhia Kabeer, Nicholas Ceglia, Mirela Andronescu, Marc J. Williams, Kieran R. Campbell, Tehmina Masud, Beixi Wang, Justina Biele, Jazmine Brimhall, David Gee, Hakwoo Lee, Jerome Ting, Allen W. Zhang, Hoa Tran, Ciara O'Flanagan, Fatemeh Dorri, Nicole Rusk, Teresa Ruiz de Algara, So Ra Lee, Brian Yu Chieh Cheng, Peter Eirew, Takako Kono, Jenifer Pham, Diljot Grewal, Daniel Lai, Richard Moore, Andrew J. Mungall, Marco A. Marra, Andrew McPherson, Alexandre Bouchard-Cote, Samuel Aparicio, Sohrab P. Shah
Summary: Progress in defining genomic fitness landscapes in cancer, particularly those associated with copy number alterations (CNAs), has been hindered by the absence of time-series single-cell sampling and temporal statistical models. This study generated a large number of genomes from long-term time-series single-cell whole-genome sequencing of breast epithelium and primary triple-negative breast cancer (TNBC) patient-derived xenografts, revealing the impact of TP53 mutation and cisplatin chemotherapy on clonal fitness dynamics defined by CNAs. The findings show that TP53 mutation alters the fitness landscape, redistributing fitness across different clones associated with distinct CNAs, and that drug treatment can lead to the emergence of drug-resistant clones while eradicating high-fitness clones in untreated settings.
Article
Multidisciplinary Sciences
Margarete A. Fabre, Jose Guilherme de Almeida, Edoardo Fiorillo, Emily Mitchell, Aristi Damaskou, Justyna Rak, Valeria Orru, Michele Marongiu, Michael Spencer Chapman, M. S. Vijayabaskar, Joanna Baxter, Claire Hardy, Federico Abascal, Nicholas Williams, Jyoti Nangalia, Inigo Martincorena, Peter J. Campbell, Eoin F. McKinney, Francesco Cucca, Moritz Gerstung, George S. Vassiliou
Summary: Clonal haematopoiesis, a common phenomenon in human tissues during aging, was studied by tracking 697 clones from 385 individuals aged 55 years or older over a median of 13 years. The study found that 92.4% of the clones expanded at a stable exponential rate, with different mutations driving different growth rates. Clones with the same mutation had growth rates differing by approximately +/- 5% per year. The study also revealed that mutations driving faster clonal growth carried a higher risk of malignant progression.
Article
Multidisciplinary Sciences
Seth M. Rudman, Sharon Greenblum, Subhash Rajpurohit, Nicolas J. Betancourt, Jinjoo Hanna, Susanne Tilk, Tuya Yokoyama, Dmitri A. Petrov, Paul Schmidt
Summary: Studying the evolution of fruit fly populations in response to natural environmental changes revealed rapid and dynamic adaptations over different generations, demonstrating the temporally dynamic nature of adaptation.
Article
Biochemical Research Methods
Ziyun Guang, Matthew Smith-Erb, Layla Oesper
Summary: In this study, a method for merging multiple tumor trees into a consensus tree was proposed, using the Weighted m-Tumor Tree Consensus Problem (W-m-TTCP) to infer tumor evolutionary histories. An algorithm called TuELiP, based on integer linear programming, was introduced to solve this problem and was shown to outperform existing methods in correctly identifying tumor trees. The importance of incorporating weights was demonstrated, with significant impacts on the consensus tree identified in a Triple-Negative Breast Cancer dataset.
Article
Biology
Sarah Sandmann, Clara Inserte, Julian Varghese
Summary: A new software package called clevRvis is developed for analyzing clonal evolution. It provides various visualization techniques, including plaice plots, which allow for easy visualization and inspection of biallelic events. The software is shown to provide new insights into tumor development through analysis of public datasets.
Article
Biochemistry & Molecular Biology
Alan Garcia-Elfring, Antoine Paccard, Timothy J. Thurman, Ben A. Wasserman, Eric P. Palkovacs, Andrew P. Hendry, Rowan D. H. Barrett
Summary: This study investigates parallel selection in six populations of threespine stickleback inhabiting bar-built estuaries undergoing seasonal environmental changes. Consistent allele frequency changes across estuaries indicate a potential role for parallel selection, with genomic changes related to osmoregulation and ion balance providing insight into early stages of adaptation in marine to freshwater transitions.
Article
Oncology
Gunjan Mandal, Subir Biswas, Carmen M. Anadon, Xiaoqing Yu, Chandler D. Gatenbee, Sandhya Prabhakaran, Kyle K. Payne, Ricardo A. Chaurio, Alexandra Martin, Patrick Innamarato, Carlos Moran, John J. Powers, Carly M. Harro, Jessica A. Mine, Kimberly B. Sprenger, Kristen E. Rigolizzo, Xuefeng Wang, Tyler J. Curiel, Paulo C. Rodriguez, Alexander R. Anderson, Ozlen Saglam, Jose R. Conejo-Garcia
Summary: This study reveals the crucial role of humoral immunity in human endometrial cancer and provides insights for the development of novel immunotherapies against this prevalent malignancy. Coordinated cellular and humoral immune responses, particularly involving B cells and IgA:plgR interactions, determine the progression of endometrial cancer and its response to treatment.
Article
Biotechnology & Applied Microbiology
Calum Gabbutt, Ryan O. Schenck, Daniel J. Weisenberger, Christopher Kimberley, Alison Berner, Jacob Househam, Eszter Lakatos, Mark Robertson-Tessi, Isabel Martin, Roshani Patel, Susan K. Clark, Andrew Latchford, Chris P. Barnes, Simon J. Leedham, Alexander R. A. Anderson, Trevor A. Graham, Darryl Shibata
Summary: Lineage tracing of human stem cells can be achieved by measuring fluctuating DNA methylation, which can serve as clocks that record cell ancestry. This study developed a mathematical model to quantitatively measure the dynamics of human adult stem cells using fluctuating DNA methylation marks. The results showed differences in the number and replacement speed of stem cells in different tissues, and also demonstrated the potential application of fluctuating methylation clocks in diseases.
NATURE BIOTECHNOLOGY
(2022)
Letter
Hematology
Guranda Chitadze, Anna Stengel, Cathrin John-Klaua, Julien Bruckmueller, Heiko Trautmann, Michaela Kotrova, Franziska Darzentas, Miriam Kelm, Karol Pal, Nikos Darzentas, Lorenz Bastian, Britta Kehden, Wiebke Wessels, Aeint-Steffen Stroeh, Hans -Heinrich Oberg, Philipp M. Altrock, Constance Baer, Manja Meggendorfer, Nicola Goekbuget, Claudia D. Baldus, Claudia Haferlach, Monika Brueggemann
Article
Biochemical Research Methods
Gregory J. Kimmel, Richard J. Beck, Xiaoqing Yu, Thomas Veith, Samuel Bakhoum, Philipp M. Altrock, Noemi Andor
Summary: Chromosome missegregations are common and can lead to drastic differences between daughter cells and parental cells. A mathematical model has been developed to account for cell-to-cell diversity caused by missegregations. The model can be used to understand selection and genotype-to-phenotype mapping, and has application in studying the upper limit of missegregation rate in cancer populations.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Oncology
Audrey R. Freischel, Jamie K. Teer, Kimberly Luddy, Jessica Cunningham, Yael Artzy-Randrup, Tamir Epstein, Kenneth Y. Tsai, Anders Berglund, John L. Cleveland, Robert J. Gillies, Joel S. Brown, Robert A. Gatenby
Summary: Evolution plays a crucial role in the initiation and progression of cancer. In addition to driver mutations, natural selection conserves genes that are necessary for optimal cancer cell fitness. By studying subtypes of lung adenocarcinoma, we identified highly mutated and highly conserved genes, which have common utility in adapting to similar tissue environments and are critical for optimal fitness. Targeting tumor-specific conserved genes may represent an effective treatment strategy.
Article
Oncology
Jill Gallaher, Maximilian Strobl, Jeffrey West, Robert Gatenby, Jingsong Zhang, Mark Robertson-Tessi, Alexander R. A. Anderson
Summary: This study proposed a framework for estimating features of metastases through tumor response dynamics in patients with metastatic castration-resistant prostate cancer undergoing adaptive androgen deprivation treatment. The size of metastases, the proportion of drug-resistant cells, and the cell turnover rate were found to affect the treatment outcomes. The number of metastases, on the other hand, did not have an impact on the treatment cycle times.
Article
Physics, Multidisciplinary
Nassim Nicholas Taleb, Jeffrey West
Summary: We apply techniques and knowledge about the stochastic properties of nonlinear responses in finance to medicine, specifically in the field of oncology, to inform dosing and intervention. We introduce the concept of antifragility and the use of risk analysis for medical problems based on the properties of nonlinear responses. We establish mathematical relationships between dosage, severity of conditions, and iatrogenics, and propose a framework for integrating nonlinearities in evidence-based oncology and clinical risk management.
Review
Biology
Jeffrey West, Fred Adler, Jill Gallaher, Maximilian Strobl, Renee Brady-Nicholls, Joel Brown, Mark Roberson-Tessi, Eunjung Kim, Robert Noble, Yannick Viossat, David Basanta, Alexander R. A. Anderson
Summary: Adaptive therapy is a dynamic cancer treatment approach that adjusts treatment decisions based on the changing tumor dynamics. It involves patient-specific dose modulation or timing to maintain high tumor burden and take advantage of treatment-sensitive subpopulations to suppress treatment-resistant subpopulations. This approach has been integrated into ongoing or planned clinical trials for various types of cancer. Mathematical modeling has played a significant role in the experimental and clinical investigation of adaptive therapy, and this paper discusses 11 open questions in this field, including integrating appropriate components into mathematical models, designing and validating dosing protocols, and addressing challenges and opportunities in clinical translation.
Article
Hematology
Erin A. Dean, Gregory J. Kimmel, Matthew J. Frank, Ali Bukhari, Nasheed M. Hossain, Michael D. Jain, Saurabh Dahiya, David B. Miklos, Philipp M. Altrock, Frederick L. Locke
Summary: We investigated the relationship between total metabolic tumor volume (MTV) on positron emission tomography (PET) scans and circulating tumor DNA (ctDNA) in patients with relapsed/refractory large B-cell lymphoma receiving axicabtagene ciloleucel (axi-cel). Our results suggested that nonprogressing hypermetabolic lesions on 1-month PET represent ongoing treatment responses, and their composition may be elucidated by concurrently examining the ctDNA.
Editorial Material
Oncology
Jad Chahoud, Alexander R. A. Anderson, Jingsong Zhang, Joel Brown, Robert A. Gatenby
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Nancy Gillis, Eric Padron, Tao Wang, Karen Chen, Jakob D. Devos, Stephen R. Spellman, Stephanie J. Lee, Carrie L. Kitko, Margaret L. Macmillan, Jeffrey West, Yi -Han Tang, Mingxiang Teng, Samantha Mcnulty, Todd E. Druley, Joseph A. Pidala, Aleksandr Lazaryan
Summary: Improved treatment options enable older patients to receive potentially curative allogeneic hematopoietic cell transplantation. An unintended risk associated with older donors is the transplantation of donor cells with clonal hematopoiesis, which may affect transplantation outcomes.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Oncology
Meghan C. Ferrall-Fairbanks, Abhishek Dhawan, Brian Johnson, Hannah Newman, Virginia Volpe, Christopher Letson, Markus Ball, Anthony M. Hunter, Maria E. Balasis, Traci Kruer, Nana Adjoa Ben-Crentsil, Jodi L. Kroeger, Robert Balderas, Rami S. Komrokji, David A. Sallman, Jing Zhang, Rafael Bejar, Philipp M. Altrock, Eric Padron
Summary: Our study reveals the differentiation trajectories of CD34+ hematopoietic stem and progenitor cells (HSPC) in chronic myelomonocytic leukemia (CMML) and identifies the monocytic-biased trajectory as an adverse feature associated with poorer outcomes. We find that cytokine receptor diversity is elevated in GMP-like cells, which contributes to the monocytic-biased state. Hypomethylating agents and hematopoietic stress are found to affect the monocytic-biased state. Our findings suggest that deconvoluting HSPC compartments and exploring therapeutic strategies to mitigate the monocytic-biased differentiation trajectory should be further investigated in other myeloid neoplasms.
BLOOD CANCER DISCOVERY
(2022)
Meeting Abstract
Oncology
Maximilian Strobl, Mehdi Damaghi, Alexandra Martin, Samantha Byrne, Mark Robertson-Tessi, Robert Gatenby, Robert Wenham, Philip Maini, Alexander R. A. Anderson
Article
Medicine, Research & Experimental
Maximilian A. R. Strobl, Jill Gallaher, Jeffrey West, Mark Robertson-Tessi, Philip K. Maini, Alexander R. A. Anderson
Summary: This theoretical study investigates the intra-tumoral competition during adaptive therapy and finds that adaptive therapy is superior to aggressive treatment in suppressing resistance. The study reveals that competition among resistant cells plays a crucial role in adaptive therapy in solid tumors.
COMMUNICATIONS MEDICINE
(2022)