Editorial Material
Biochemistry & Molecular Biology
Haixi Yan, Maxime Tarabichi, Nicholas McGranahan, Peter Van Loo
Summary: Accurately identifying the subclones that make up tumors is crucial for understanding cancer biology. In this article, Satas et al. examine mutations with an evolutionary perspective to decipher the composition of tumors.
Article
Biochemical Research Methods
Maxime Tarabichi, Adriana Salcedo, Amit G. Deshwar, Maire Ni Leathlobhair, Jeff Wintersinger, David C. Wedge, Peter Van Loo, Quaid D. Morris, Paul C. Boutros
Summary: The Perspective reviews computational methods for subclonal reconstruction in cancer evolution studies, outlining complex approaches and best practices for analysis. It provides insight into clonality and mutational processes, identifying underlying assumptions and uncertainties in each step. This guide serves as a pragmatic resource for the growing user community of subclonal reconstruction methods.
Article
Oncology
Nina Mueller, Carina Lorenz, Jenny Ostendorp, Felix S. Heisel, Ulrich P. Friese, Maria Cartolano, Dennis Plenker, Hannah Tumbrink, Alena Heimsoeth, Philipp Baedeker, Jonathan Weiss, Sandra Ortiz-Cuaran, Reinhard Buettner, Martin Peifer, Roman K. Thomas, Martin L. Sos, Johannes Berg, Johannes Braegelmann
Summary: The emergence of resistance to targeted therapies poses a challenge to their efficacy. This study presents a strategy to identify and understand resistant subpopulations in a lung cancer cell line, leading to the development of a combination therapy that effectively eradicates resistant clones. The study also reveals the presence of a small fraction of drug-tolerant cancer cells, which can be targeted by exploiting induced collateral sensitivity. Overall, this research highlights the importance of rational combination therapies in overcoming resistance in cancer treatment.
Article
Cell Biology
Haider Tari, Ketty Kessler, Nick Trahearn, Benjamin Werner, Maria Vinci, Chris Jones, Andrea Sottoriva
Summary: In this study, a Bayesian inference framework was used to quantify spatial subclonal interactions in diffuse midline gliomas (DMGs). The study found that interactions between different subclones may enhance tumor invasion.
Article
Forestry
Wai Pak Ng, Frank T. van Manen, Stuart P. Sharp, Siew Te Wong, Shyamala Ratnayeke
Summary: Commercial forest plantations globally meet the increasing demand for wood products, potentially contributing to tropical forest conservation. A study in Sabah, East Malaysia showed positive associations between natural forest area and mammal species richness, as well as an increase in threatened mammals detections near natural forest and Acacia plantations. Acacia plantations support a diversity of mammal species, especially when adjacent to natural forest or mangrove forests, highlighting the importance of habitat mosaic and conservation efforts in industrial plantations.
FOREST ECOLOGY AND MANAGEMENT
(2021)
Article
Biochemistry & Molecular Biology
Daeun Ryu, Tae-Min Kim, Yun-Hee Lee, U-Syn Ha
Summary: Longitudinal tumor sequencing of recurrent bladder cancer (BC) was performed using whole-exome and transcriptome sequencing. The study revealed the genetic makeup associated with APOBEC deaminase activity was accomplished early in cancer evolution and that chemotherapy often led to clonal sweeps. Transcriptome sequencing also showed frequent subtype switching during tumor progression. This research provides insights into BC heterogeneity in terms of somatic mutations, cell clones, and transcriptome-based tumor subtypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Anuradha Jagadeesan, S. Sunna Ebenesersdottir, Valdis B. Gudmundsdottir, Elisabet Linda Thordardottir, Kristjan H. S. Moore, Agnar Helgason
Summary: HaploGrouper is a versatile software that can classify haplotypes into haplogroups based on a known phylogenetic tree, providing flexibility and accuracy for assigning haplogroups to any type of haplotypes from any species.
Article
Energy & Fuels
He Wang, Xi Zhang, Yali Ma, Mengke Wang, Jun Wang
Summary: A facile, universal, ecofriendly, and energy-saving approach to synthesize high-quality 2D hybrid halide-layered perovskite crystals at room temperature is reported. By involving potassium iodide to the reaction, potassium ions can assist both the crystal growth and surface passivation, improving their stability and passivated trap states.
Review
Cell Biology
Xiao-Mei Zhang, De-Gao Chen, Shengwen Calvin Li, Bo Zhu, Zhong-Jun Li
Summary: Macrophages play crucial roles in cancer, with TAMs being highly plastic and heterogeneous in response to microenvironmental cues. The ontogeny and metabolic remodeling of TAMs contribute to their functional heterogeneity, making them potential targets for cancer immunotherapy.
Review
Oncology
Ioanna Mavrommati, Flora Johnson, Gloria Echeverria, Rachael Natrajan
Summary: This review focuses on the recent advances in understanding the epigenetic and transcriptomic changes in breast cancer at the single-cell level, and highlights the utility of single-cell tracing and molecular barcoding methodologies in assessing disease evolution and therapy response. Integrating single-cell profiling from patient samples with results from preclinical models can untangle complexities of the disease and identify biomarkers for disease progression, potentially uncovering new targetable vulnerabilities in breast cancer.
Article
Statistics & Probability
Shai He, Aaron Schein, Vishal Sarsani, Patrick Flaherty
Summary: There are distinguishing features of cancer that can be driven by specific genetic mutations, but individual tumors often exhibit genetic heterogeneity. This study aims to infer tumor subpopulation genotypes and distributions within individual tumors by integrating single-cell and bulk sequencing data, which is crucial for personalized targeted therapy and post-treatment monitoring. The proposed model shows improved inference quality and performance compared to standard methods, as demonstrated in simulation and real cancer sequencing datasets.
ANNALS OF APPLIED STATISTICS
(2021)
Article
Chemistry, Multidisciplinary
Yongxin Chen, Yongjun Wang, Luming Yang
Summary: Tor performs better than other anonymous communication tools in protecting users' privacy, but it can still be de-anonymized by website fingerprinting attacks. This paper proposes a new method to address the data shortage issue and achieves significant performance improvement.
APPLIED SCIENCES-BASEL
(2022)
Article
Multidisciplinary Sciences
Darlan C. Minussi, Michael D. Nicholson, Hanghui Ye, Alexander Davis, Kaile Wang, Toby Baker, Maxime Tarabichi, Emi Sei, Haowei Du, Mashiat Rabbani, Cheng Peng, Min Hu, Shanshan Bai, Yu-wei Lin, Aislyn Schalck, Asha Multani, Jin Ma, Thomas O. McDonald, Anna Casasent, Angelica Barrera, Hui Chen, Bora Lim, Banu Arun, Funda Meric-Bernstam, Peter Van Loo, Franziska Michor, Nicholas E. Navin
Summary: Breast tumors and cell lines consist of numerous subclones organized into a few major superclones. Following clonal TP53 mutations, loss-of-heterozygosity events, and genome doubling, primary tumors undergo a period of transient genomic instability, with ongoing copy number evolution during expansion. Subcloned daughter cells demonstrate genomic rediversification, showing that triple-negative breast cancers continually evolve chromosome aberrations and maintain subclonal diversity during primary tumor growth.
Article
Engineering, Mechanical
Jing Zhao, Tong Wu, Ziqiang Zhang, Xiaohui Li, Weihui Liu
Summary: This paper proposes a novel method for generating configurations based on iterative concepts and establishes a tree-evolution kinematic synthesis framework. By researching the performance distribution characteristics of the 'tree' and developing tree-evolution strategies, a serial robot configuration model with hyperparameters is proposed.
MECHANISM AND MACHINE THEORY
(2021)
Article
Geosciences, Multidisciplinary
Luc S. Doucet, Michael G. Tetley, Zheng-Xiang Li, Yebo Liu, Hamed Gamaleldien
Summary: This study discusses the use of basalt geochemistry to understand different tectonic settings and mantle processes in Earth's history, highlighting challenges with traditional discrimination diagram approaches. By utilizing a big-data method, different types of basalts formed in various tectonic environments were successfully identified, presenting a novel chemical 'fingerprinting' approach for more accurate discrimination.
EARTH-SCIENCE REVIEWS
(2022)
Article
Medical Laboratory Technology
Lina Irshaid, Jonathan Bleiberg, Ethan Weinberger, James Garritano, Rory M. Shallis, Jonathan Patsenker, Ofir Lindenbaum, Yuval Kluger, Samuel G. Katz, Mina L. Xu
Summary: This study aimed to investigate the accuracy and reproducibility of a trained convolutional neural network in identifying large cell transformation (LCT) in bone marrow biopsy. The results showed that certain morphologic criteria were significantly correlated with LCT, and the machine learning tools demonstrated better reproducibility and predictive ability compared to pathologists' estimates, providing a new method for the diagnosis of LCT in bone marrow biopsy.
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Esen Sefik, Benjamin Israelow, Haris Mirza, Jun Zhao, Rihao Qu, Eleanna Kaffe, Eric Song, Stephanie Halene, Eric Meffre, Yuval Kluger, Michel Nussenzweig, Craig B. Wilen, Akiko Iwasaki, Richard A. Flavell
Summary: This study introduces a humanized mouse model of COVID-19 that replicates the immune response and pathological features of the infection, providing a valuable tool for investigating disease mechanisms and treatment options.
NATURE BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
George C. Linderman, Jun Zhao, Manolis Roulis, Piotr Bielecki, Richard A. Flavell, Boaz Nadler, Yuval Kluger
Summary: A key challenge in analyzing single cell RNA-sequencing data is the presence of a large number of false zeros. The authors propose a method based on low-rank matrix approximation to impute these false zeros while preserving true zeros. The advantages of this method are demonstrated on simulated and biological datasets.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Rihao Qu, Khusali Gupta, Danni Dong, Yiqun Jiang, Boris Landa, Charles Saez, Gwendolyn Strickland, Jonathan Levinsohn, Pei-lun Weng, M. Mark Taketo, Yuval Kluger, Peggy Myung
Summary: This study designed a computational approach to resolve signals and cell behaviors in organogenesis, revealing the role of Wnt/β-catenin and SHH signaling gradients in cell proliferation and spatial patterning.
DEVELOPMENTAL CELL
(2022)
Article
Computer Science, Artificial Intelligence
Uri Shaham, Ofir Lindenbaum, Jonathan Svirsky, Yuval Kluger
Summary: Modern datasets often contain large subsets of correlated features and nuisance features. We propose an unsupervised feature selection method that avoids selecting nuisance features using the Laplacian score criterion, and we employ an autoencoder architecture to handle correlated features. Experimental results demonstrate the superiority of our approach.
Article
Medicine, Research & Experimental
Shelli F. Farhadian, Ofir Lindenbaum, Jun Zhao, Michael J. Corley, Yunju Im, Hannah Walsh, Alyssa Vecchio, Rolando Garcia-Milian, Jennifer Chiarella, Michelle Chintanaphol, Rachela Calvi, Guilin Wang, Lishomwa C. Ndhlovu, Jennifer Yoon, Diane Trotta, Shuangge Ma, Yuval Kluger, Serena Spudich
Summary: People with HIV on antiretroviral therapy experience neurological impairment, possibly due to viral or neuroimmune causes. Single-cell analysis of paired cerebrospinal fluid and peripheral blood revealed the production of HIV-1 RNA in central memory CD4+ T cells in the cerebrospinal fluid, as well as a higher frequency of infected cells in the cerebrospinal fluid compared to the blood. Additionally, rare microglia-like cells in the cerebrospinal fluid were identified using a reliable cell surface marker, CD204. Abnormal CD8+ T cell activation was found to be prevalent in the cerebrospinal fluid of people with HIV, suggesting ongoing CNS viral persistence and compartmentalized neuroimmune effects.
Article
Hematology
Jingjing Ren, Rihao Qu, Nur-Taz Rahman, Julia M. Lewis, Amber Loren Ong King, Xiaofeng Liao, Fatima N. Mirza, Kacie R. Carlson, Yaqing Huang, Scott Gigante, Benjamin Evans, Barani Kumar Rajendran, Suzanne Xu, Guilin Wang, Francine M. Foss, William Damsky, Yuval Kluger, Smita Krishnaswamy, Michael Girardi
Summary: The incidence of cutaneous T-cell lymphoma (CTCL) increases with age and blood involvement is associated with a worse prognosis. In this study, we analyzed the transcriptomic profiles and T-cell receptor (TCR) sequences of CD4+ T cells from CTCL patients, revealing common features of the disease and potential therapeutic targets.
Letter
Cardiac & Cardiovascular Systems
Siting Zhu, Anh Nguyen, Jing Pang, Jun Zhao, Ze'e Chen, Zhengyu Liang, Yusu Gu, Helen Huynh, Yutong Bao, Sharon Lee, Yuval Kluger, Kunfu Ouyang, Sylvia M. Evans, Xi Fang
Article
Computer Science, Interdisciplinary Applications
James Garritano, Yuval Kluger, Vladimir Rokhlin, Kirill Serkh
Summary: In this paper, an efficient algorithm for evaluating the azimuthal Fourier components of the Green's function for the Helmholtz equation in cylindrical coordinates is developed. The algorithm is essential for solving electromagnetic scattering problems and is not affected by the proximity of the source and target, the magnitude or complexity of the wavenumber. Furthermore, the algorithm can be easily parallelized.
JOURNAL OF COMPUTATIONAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Rihao Qu, Yuval Kluger, Junchen Yang, Jun Zhao, David A. Hafler, Diane S. Krause, Alexey Bersenev, Marcus Bosenberg, Michael Hurwitz, Liliana Lucca, Harriet M. Kluger
Summary: This study investigates the clonal cell expansion and persistence in adoptive cell therapy (ACT) using tumor infiltrating lymphocytes (TIL). The researchers performed single-cell RNA and T-Cell Receptor (TCR) sequencing on blood and tumor samples from a non-responsive ACT patient. They found varying clonal expansion during the preparation of the ACT product, with only one expanded clone preserved. The preserved clone persisted and remained activated for five months, while the contracted clones showed features of exhaustion and apoptosis. Analysis of additional ACT-treated patients and differentiation between viral- and tumor-specificity is recommended.
Article
Multidisciplinary Sciences
Di Zhang, Yanxiang Deng, Petra Kukanja, Eneritz Agirre, Marek Bartosovic, Mingze Dong, Cong Ma, Sai Ma, Graham Su, Shuozhen Bao, Yang Liu, Yang Xiao, Gorazd B. Rosoklija, Andrew J. Dwork, J. John Mann, Kam W. Leong, Maura Boldrini, Liya Wang, Maximilian Haeussler, Benjamin J. Raphael, Yuval Kluger, Goncalo Castelo-Branco, Rong Fan
Summary: Emerging spatial technologies such as spatial transcriptomics and spatial epigenomics have become powerful tools in profiling cellular states in tissue contexts. However, current methods only capture one layer of omics information at a time, limiting the examination of mechanistic relationships in molecular biology. In this study, two technologies are presented for joint profiling of the epigenome and transcriptome at a genome-wide, spatially resolved, and near-single-cell resolution. These technologies provide new insights into spatial epigenetic priming, differentiation, and gene regulation within tissue architecture.
Article
Cell Biology
Inamul Kabir, Xinbo Zhang, Jui M. M. Dave, Raja Chakraborty, Rihao Qu, Rachana R. R. Chandran, Aglaia Ntokou, Eunate Gallardo-Vara, Binod Aryal, Noemi Rotllan, Rolando Garcia-Milian, John Hwa, Yuval Kluger, Kathleen A. A. Martin, Carlos Fernandez-Hernando, Daniel M. M. Greif
Summary: Aging is a major risk factor for atherosclerosis, but its effect on smooth muscle cell clonality is unclear. Researchers found that aged bone marrow-derived cells can induce non-cell autonomous smooth muscle cell polyclonality, exacerbating atherosclerosis. This occurs because levels of TET2, a gene that regulates integrin beta(3), are decreased in myeloid cells from aged mice and humans, resulting in increased TNF alpha signaling. TNF alpha promotes smooth muscle cell proliferation, as well as the recruitment and expansion of multiple smooth muscle cell progenitors into the atherosclerotic plaque. However, overexpression of integrin beta(3) in aged bone marrow can preserve the dominance of a single smooth muscle cell progenitor and reduce plaque burden. These findings provide insights into the molecular mechanism of aged macrophage-induced smooth muscle cell polyclonality and atherogenesis, and suggest potential therapeutic strategies.
Article
Biochemical Research Methods
Micha Sam Brickman Raredon, Junchen Yang, Neeharika Kothapalli, Wesley Lewis, Naftali Kaminski, Laura E. Niklason, Yuval Kluger
Summary: NICHES is a tool that explores extracellular signaling at the truly single-cell level by embedding ligand-receptor signal proxies to visualize heterogeneous signaling archetypes within and between cell clusters as well as across experimental conditions. It can be applied to spatial transcriptomic data to reflect local cellular microenvironment, is compatible with existing single-cell packages, and allows rapid, flexible analysis of cell-cell signaling at single-cell resolution.
Article
Cell Biology
Patty J. Lee, Christopher C. Benz, Philip Blood, Katy Boerner, Judith Campisi, Feng Chen, Heike Daldrup-Link, Phil De Jager, Li Ding, Francesca E. Duncan, Oliver Eickelberg, Rong Fan, Toren Finkel, David Furman, Vesna Garovic, Nils Gehlenborg, Carolyn Glass, Indra Heckenbach, Ziv-Bar Joseph, Pragati Katiyar, So-Jin Kim, Melanie Koenigshoff, George A. Kuchel, Haesung Lee, Jun Hee Lee, Jian Ma, Qin Ma, Simon Melov, Kay Metis, Ana L. Mora, Nicolas Musi, Nicola Neretti, Joao F. Passos, Irfan Rahman, Juan Carlos Rivera-Mulia, Paul Robson, Mauricio Rojas, Ananda L. Roy, Morten Scheibye-Knudsen, Birgit Schilling, Pixu Shi, Jonathan C. Silverstein, Vidyani Suryadevara, Jichun Xie, Jinhua Wang, A. Ian Wong, Laura J. Niedernhofer, Siyuan (Steven) Wang, Hannah Anvari, Julia Balough, Christopher Benz, Joanna Bons, Boris Brenerman, William Evans, Akos Gerencser, Heather Gregory, Malene Hansen, Jamie Justice, Pankaj Kapahi, Natalia Murad, Amy O'Broin, Mary Ellen Pavone, Mark Powell, Gary Scott, Elisheva Shanes, Mahalakshmi Shankaran, Eric Verdin, Daniel Winer, Fei Wu, Andrew Adams, Philip D. Blood, Andreas Bueckle, Ivan Cao-Berg, Hao Chen, Michael Davis, Shane Filus, Yuhan Hao, Austin Hartman, Euxhen Hasanaj, Jesse Helfer, Bruce Herr, Ziv Bar Joseph, Gesmira Molla, Gloria Mou, Juan Puerto, Ellen M. Quardokus, Alexander J. Ropelewski, Matt Ruffalo, Rahul Satija, Melissa Schwenk, Robin Scibek, William Shirey, Max Sibilla, Joel Welling, Zhou Yuan, Richard Bonneau, Angela Christiano, Benjamin Izar, Vilas Menon, David M. Owens, Hemali Phatnani, Colin Smith, Yousin Suh, Andrew F. Teich, Valerie Bekker, Cliburn Chan, Elias Coutavas, Matthew G. Hartwig, Zhicheng Ji, Andrew B. Nixon, Zhixun Dou, Jayaraj Rajagopal, Nikolai Slavov, David Holmes, Diana Jurk, James L. Kirkland, Anthony Lagnado, Tamara Tchkonia, Kristin Abraham, Amanda Dibattista, Yih-Woei Fridell, T. Kevin Howcroft, Chamelli Jhappan, Viviana Perez Montes, Mercy Prabhudas, Haluk Resat, Veronica Taylor, Manoj Kumar, Francisco Cigarroa, Rachel Cohn, Tiffany M. Cortes, Elise Courtois, Jeffrey Chuang, Monica Dave, Sergii Domanskyi, Elizabeth Ann Lieser Enninga, Giray Naim Eryilmaz, Sara E. Espinoza, Jon Gelfond, James Kirkland, Chia-Ling Kuo, Julia S. Lehman, Cristina Aguayo-Mazzucato, Alexander Meves, Meenakshi Rani, Shane Sanders, Asa Thibodeau, Stefan G. Tullius, Duygu Ucar, Brian White, Qian Wu, Ming Xu, Seiji Yamaguchi, Naziheh Assarzadegan, Chun-Seok Cho, Irene Hwang, Yongha Hwang, Jingyue Xi, Oyedele A. Adeyi, Constantin F. Aliferis, Alessandro Bartolomucci, Xiao Dong, Mickayla J. DuFresne-To, Sayeed Ikramuddin, Steve G. Johnson, Andrew C. Nelson, Xavier S. Revelo, Claudia Trevilla-Garcia, John M. Sedivy, Elizabeth L. Thompson, Paul D. Robbins, Jinhua Wang, Katherine M. Aird, Jonathan K. Alder, Delphine Beaulieu, Marta Bueno, Jazmin Calyeca, Julian A. Chamucero-Millaris, Stephen Y. Chan, Dongjun Chung, Anthony Corbett, Vera Gorbunova, Kymberly M. Gowdy, Aditi Gurkar, Jeffrey C. Horowitz, Qianjiang Hu, Gagandeep Kaur, Timur O. Khaliullin, Robert Lafyatis, Serafina Lanna, Dongmei Li, Anjun Ma, Alison Morris, Thivanka M. Muthumalage, Victor Peters, Gloria S. Pryhuber, Brenda F. Reader, Lorena Rosas, John C. Sembrat, Sadiya Shaikh, Hangchuan Shi, Sean D. Stacey, Claudette St Croix, Cankun Wang, Qixin Wang, Andrew Watts, Liangcai Gu, Yiing Lin, Peter S. Rabinovitch, Mariya T. Sweetwyne, Maxim N. Artyomov, Samuel J. Ballentine, Milan G. Chheda, Sherri R. Davies, John F. DiPersio, Ryan C. Fields, James A. J. Fitzpatrick, Robert S. Fulton, Shin-ichiro Imai, Sanjay Jain, Tao Ju, Vladimir M. Kushnir, Daniel C. Link, Michael Ben Major, Stephen T. Oh, Daniel Rapp, Michael P. Rettig, Shelia A. Stewart, Deborah J. Veis, Kiran R. Vij, Michael C. Wendl, Matthew A. Wyczalkowski, Joseph E. Craft, Archibald Enninful, Negin Farzad, Peter Gershkovich, Stephanie Halene, Yuval Kluger, Jennifer VanOudenhove, Mina Xu, Junchen Yang, Mingyu Yang
Summary: Cells respond to stress by undergoing senescence, and the heterogeneity of senescent cells and their secretory phenotype need further characterization. The Cellular Senescence Network (SenNet) was established to create a map of senescent cells across the human lifespan and improve diagnostic and therapeutic approaches.
Meeting Abstract
Dermatology
J. Ren, R. Qu, N. Rahman, J. Lewis, A. King, X. Liao
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)