Article
Genetics & Heredity
Tianyun Zhang, Hanying Jia, Tairan Song, Lin Lv, Doga C. Gulhan, Haishuai Wang, Wei Guo, Ruibin Xi, Hongshan Guo, Ning Shen
Summary: This study proposes a computational framework called RESA for identifying expressed somatic mutations from single-cell RNA sequencing data. Through testing on simulated and real datasets, the method demonstrates high accuracy and performance, which is of great significance for mutational analysis.
Article
Biochemical Research Methods
Sini Junttila, Johannes Smolander, Laura L. Elo
Summary: This study compared 18 methods for identifying differential states (DS) changes between conditions in multisubject scRNA-seq data, and found that pseudobulk methods and mixed models performed best, showing superior statistical performance compared to naive single-cell methods.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Chen Su, Rong Yu, Xiaoquan Hong, Panpan Zhang, Yingying Guo, Jian-Chun Cai, Jingjing Hou
Summary: Gastric cancer (GC) is a common malignant tumor and the fourth leading cause of tumor-related mortality worldwide. This study utilized scRNA-Seq and bulk RNA-Seq data to identify hub genes in tumor-infiltrating B cells (TIBs) in GC, and found that CXCR4 is highly expressed by TIBs and may serve as a hub gene and potential therapeutic target for these immune cells in GC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Daishin Ueno, Shotaro Yamasaki, Ko Kato
Summary: This review discusses the findings and limitations of RNA degradation sequencing methods, and suggests further experiments needed to accurately understand RNA degradation intermediates. It provides direction for future research on RNA degradation and serves as a reference for RNA degradome studies in other species.
Review
Cell Biology
Suman Singh, Sharmishtha Shyamal, Amaresh C. Panda
Summary: In the past decade, there has been a significant increase in novel RNA molecules and their complexity in gene regulation. RNA-RNA interactions play a critical role in cellular events by regulating the biogenesis and function of RNA molecules. Understanding the mechanisms and functions of RNA-RNA interactions is essential for eukaryotes. The advent of high-throughput RNA-sequencing technologies has revolutionized the study of RNA-RNA interactions.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
Article
Biochemical Research Methods
Lihong Zhao, Cong Yan, Shuzhen Kong, Tao Jia, Zhaowei Chu, Li Yang, Jian Wu, Songmei Geng, Kun Guo
Summary: CAP has more significant biological effects on melanoma cells than on HaCaT cells by inhibiting proliferation and promoting apoptosis. CAP can selectively kill melanoma cells and has good biosafety cytologically. Besides apoptosis, CAP can induce cell death via autophagy and necroptosis.
JOURNAL OF BIOPHOTONICS
(2022)
Article
Immunology
Guohong Gao, Aijun Deng, Shan Liang, Shengsheng Liu, Xinyi Fu, Xiaoyan Zhao, Zhilong Yu
Summary: This study explored the tumor heterogeneity of uveal melanoma (UM) through RNA sequencing and single-cell RNA sequencing, identifying different immune subtypes and cell groups in UM. The findings provided valuable information about UM's immune characteristics and expression patterns of transcription factors in different cell types.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Kristiyan Kanev, Patrick Roelli, Ming Wu, Christine Wurmser, Mauro Delorenzi, Michael W. Pfaffl, Dietmar Zehn
Summary: Single-cell RNA-seq offers the opportunity to improve the efficacy of T-cell based immunotherapy. The plate-based method developed by the authors for cytotoxic T cell profiling captures a higher number of transcripts and detects genes with increased dynamic range compared to droplet-based methods.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Jiadi Zhu, Youlong Yang
Summary: In this study, we propose a novel and fast method called scMEB for detecting single-cell differentially expressed genes (DEGs) without prior cell clustering. The scMEB method utilizes a small part of known non-DEGs to build a minimum enclosing ball and defines DEGs based on their distance from the center of the hypersphere in a feature space. Experimental comparisons on 11 real datasets showed that scMEB outperformed other methods in terms of cell clustering, prediction of genes with biological functions, and identification of marker genes. Furthermore, scMEB was significantly faster than alternative methods, making it highly effective for DEG discovery in high-throughput scRNA-seq data. We have developed a software package, scMEB, for implementing the proposed method, which is available at https://github.com/FocusPaka/scMEB.
Article
Biochemistry & Molecular Biology
Ivanina Mutisheva, Steve Robatel, Lukas Bariswyl, Mirjam Schenk
Summary: The study aimed to develop a method that allows cells to be fixed and stored prior to FACS sorting for scRNA-seq without compromising the quality of the results. The study focused on pancreatic ductal adenocarcinoma samples and addressed the issue of preserving as many living cells as possible during tissue processing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Yi-Dan Liu, Ying-Ting Zhu, Yun-Hong Shi, Xiu-Xing Liu, Wen-Ru Su, Ye-Hong Zhuo
Summary: Adult neural stem cells (NSCs) are confined to specific regions of the mammalian brain and possess the ability to self-renew and differentiate into various cell lineages. Single-cell RNA sequencing technology has provided detailed insights into the heterogeneity of NSCs and their transcriptional changes in aging and brain tumors. Understanding NSCs in both physiological and pathological contexts is crucial for rejuvenating the aging brain and restoring normal brain function in neurological disorders.
STEM CELLS AND DEVELOPMENT
(2023)
Letter
Oncology
Marius Bill, Krzysztof Mrozek, Brian Giacopelli, Jessica Kohlschmidt, Deedra Nicolet, Dimitrios Papaioannou, Ann-Kathrin Eisfeld, Jonathan E. Kolitz, Bayard L. Powell, Andrew J. Carroll, Richard M. Stone, Ramiro Garzon, John C. Byrd, Clara D. Bloomfield, Christopher C. Oakes
Summary: The novel knowledge bank (KB) approach utilizing machine learning has shown promising predictive value for individual patient outcomes in acute myeloid leukemia (AML). The KB algorithm outperformed traditional risk classifications, especially in predicting overall survival probability, non-remission death, and certain genetic factors may further enhance its predictive accuracy.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Vincenzo Maria Perriello, Ilaria Gionfriddo, Roberta Rossi, Francesca Milano, Federica Mezzasoma, Andrea Marra, Orietta Spinelli, Alessandro Rambaldi, Ombretta Annibali, Giuseppe Avvisati, Francesco Di Raimondo, Stefano Ascani, Brunangelo Falini, Maria Paola Martelli, Lorenzo Brunetti
Summary: One-third of adult AML patients have NPM1 mutations, with high expression of CD123 identified as a potential target for therapy in NPM1-mutated leukemic cells, particularly in CD34(+)CD38(-) cells. Targeting CD123 may be effective for treating NPM1-mutated AML, especially in combination with FLT3 mutations.
Article
Cell Biology
Yaqing Zhou, Sheng Zhang, Wenfeng Ji, Xiongkang Gan, Lei Hua, Can Hou, Jiaxin Chen, Yanjun Wang, Shu He, Hanxiao Zhou, Enzhi Jia
Summary: This study identified differentially expressed lncRNAs and mRNAs in atherosclerosis through RNA sequencing and validated their roles in smooth muscle cells, providing new targets for the diagnosis and treatment of atherosclerosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemical Research Methods
M. E. Nelson, S. G. Riva, A. Cvejic
Summary: Single-cell RNA-sequencing is revolutionizing the study of cellular and tissue-wide heterogeneity. SMaSH is a new computational framework that can extract key marker genes from single-cell RNA-sequencing data, which characterize highly-specific and niche populations of cells.
BMC BIOINFORMATICS
(2022)
Article
Hematology
Margaret A. Ferris, Amanda M. Smith, Sharon E. Heath, Eric J. Duncavage, Matthew Oberley, David Freyer, Robert Wynn, Sofia Douzgou, John M. Maris, Anne F. Reilly, Melinda D. Wu, Florence Choo, Roel B. Fiets, Saskia Koene, David H. Spencer, Christopher A. Miller, Marwan Shinawi, Timothy J. Ley
Letter
Hematology
Matthew J. Christopher, Casey D. S. Katerndahl, Hayley R. LeBlanc, Tyler T. Elmendorf, Vaishali Basu, Margery Gang, Andrew J. Menssen, David H. Spencer, Eric J. Duncavage, Shamika Ketkar, Lukas D. Wartman, Sai Mukund Ramakrishnan, Christopher A. Miller, Timothy J. Ley
Article
Pathology
Christopher A. Miller, Jason R. Walker, Travis L. Jensen, William F. Hooper, Robert S. Fulton, Jeffrey S. Painter, Mikkael A. Sekeres, Timothy J. Ley, David H. Spencer, Johannes B. Goll, Matthew J. Walter
Summary: This study provides a detailed analysis of somatic mutations in the U2AF1 gene and highlights the impact of changes in the GRCh38 reference build on mutation detection. It proposes a modified GRCh38 reference build with unchanged coordinates as a solution to improve mutation detection.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
Article
Oncology
Elisabeth R. Wilson, Nichole M. Helton, Sharon E. Heath, Robert S. Fulton, Jacqueline E. Payton, John S. Welch, Matthew J. Walter, Peter Westervelt, John F. DiPersio, Daniel C. Link, Christopher A. Miller, Timothy J. Ley, David H. Spencer
Summary: Recurrent mutations in IDH1 or IDH2 in AML lead to increased DNA methylation, especially at focal regions, potentially due to inhibition of TET-mediated demethylation. This hypermethylation is significantly enriched in enhancers interacting with genes involved in normal hematopoiesis and AML. The balance between DNA methylation and demethylation pathways at enhancers may play a role in AML pathogenesis in IDH-mutant AML.
Article
Hematology
Pawan Upadhyay, Jeremy Beales, Nakul M. Shah, Agata Gruszczynska, Christopher A. Miller, Allegra A. Petti, Sai Mukund Ramakrishnan, Daniel C. Link, Timothy J. Ley, John S. Welch
Summary: The molecular events responsible for decitabine responses in myelodysplastic syndrome and acute myeloid leukemia patients remain poorly understood. In vivo treatment with decitabine induced global, reversible hypomethylation after 10 days, associated with interferon-induced pathways, expression of endogenous retroviral elements, and inhibition of erythroid-related transcripts. Clinical responses were not correlated with epigenetic or transcriptional signatures, but global hypomethylation by decitabine and reversal of erythroid-related pathways at relapse were observed.
EXPERIMENTAL HEMATOLOGY
(2022)
Correction
Multidisciplinary Sciences
Allegra A. Petti, Stephen R. Williams, Christopher A. Miller, Ian T. Fiddes, Sridhar N. Srivatsan, David Y. Chen, Catrina C. Fronick, Robert S. Fulton, Deanna M. Church, Timothy J. Ley
NATURE COMMUNICATIONS
(2022)
Article
Dermatology
Lauren K. Shea, Neal S. Akhave, Leslie A. Sutton, Leigh A. Compton, Conner York, Sai Mukund Ramakrishnan, Christopher A. Miller, Lukas D. Wartman, David Y. Chen
Summary: Cutaneous squamous cell carcinoma (cSCC) has a high mutation burden, mainly due to UV light exposure. KDM6A is frequently mutated in cSCC and acts as a tumor suppressor. In mice, the deficiency of both Kdm6a and Trp53 leads to spontaneous cSCC development, with recurrent mutations found in Ncstn and Vcan.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Oncology
Ruiyi Tian, Brian Wiley, Jie Liu, Xiaoyu Zong, Buu Truong, Stephanie Zhao, Md Mesbah Uddin, Abhishek Niroula, Christopher A. Miller, Semanti Mukherjee, Brendan T. Heiden, Jingqin Luo, Varun Puri, Benjamin D. Kozower, Matthew J. Walter, Li Ding, Daniel C. Link, Christopher Amos, Benjamin L. Ebert, Ramaswamy Govindan, Pradeep Natarajan, Kelly L. Bolton, Yin Cao
Summary: This study prospectively examined the association between clonal hematopoiesis (CH) and subsequent risk of lung cancer. It found that CH is independently associated with increased risk of lung cancer, regardless of known risk factors.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Eileen Wedge, Ulvi Ahmadov, Thomas B. Hansen, Zongliang Gao, Morten Tulstrup, Christophe Come, Sridhar Nonavinkere Srivatsan, Tanzir Ahmed, Jakob S. Jespersen, Balthasar C. Schlotmann, Claudia Schollkopf, Klas Raaschou-Jensen, Niels Odum, Jorgen Kjems, Rasmus O. Bak, Matthew J. Walter, Kirsten Gronbaek, Lasse S. Kristensen
Summary: Mutations in the U2AF1 gene are associated with a higher occurrence of myelodysplastic neoplasms (MDS) and a worse prognosis, but the exact molecular mechanisms are not fully understood. This study found that U2AF1 mutations may impact circRNA production, leading to increased cancer development. Increased circRNA expression levels were observed in cells and patient samples with U2AF1 mutations, suggesting a potential role of circRNA as a biomarker and therapeutic target in MDS.
Article
Medicine, Research & Experimental
David Y. Chen, Leslie A. Sutton, Sai Mukund Ramakrishnan, Eric J. Duncavage, Sharon E. Heath, Leigh A. Compton, Christopher A. Miller, Timothy J. Ley
Summary: Alterations in epigenetic regulators are increasingly recognized as early events in tumorigenesis. Patients with acquired or inherited variants in epigenetic regulators may be at increased risk for developing multiple types of cancer. We report the case of an adult DOS patient with a germline DNMT3A loss-of-function mutation, who developed an early-onset melanoma with regional lymph node metastatic disease. Exome sequencing of the primary tumor identified an additional acquired, missense DNMT3A mutation in the dominant tumor clone, suggesting that the loss of DNMT3A function was relevant for the development of this tumor.
COLD SPRING HARBOR MOLECULAR CASE STUDIES
(2023)
Review
Immunology
Noah Earland, Wubing Zhang, Abul Usmani, Aishwarya Nene, Antonella Bacchiocchi, David Y. Chen, Mario Sznol, Ruth Halaban, Aadel A. Chaudhuri, Aaron M. Newman
Summary: Immune-related toxicities, also known as immune-related adverse events (irAEs), are common side effects in cancer patients treated with immune checkpoint inhibitors (ICIs). These side effects can range from mild to severe, leading to hospitalization, high-dose corticosteroid treatment, discontinuation of ICIs, and even death. Through recent research, we have identified two baseline features - elevated activated CD4 effector memory T-cell abundance and TCR diversity - in circulation that are associated with severe irAE development in advanced melanoma patients. This understanding provides a foundation for improving irAE prediction and prevention, ultimately reducing morbidity and mortality associated with ICIs.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Oncology
Allegra A. Petti, Saad M. Khan, Ziheng Xu, Nichole Helton, Catrina C. Fronick, Robert Fulton, Sai M. Ramakrishnan, Sridhar Nonavinkere Srivatsan, Sharon E. Heath, Peter Westervelt, Jacqueline E. Payton, Matthew J. Walter, Daniel C. Link, John DiPersio, Christopher Miller, Timothy J. Ley
Summary: This study investigates the clonal and transcriptional adaptations in patients with acute myeloid leukemia (AML) after relapse. The researchers collected presentation and relapse samples from six AML cases and performed whole-genome sequencing and single-cell RNA sequencing. The study reveals the coevolution of genetic and transcriptional heterogeneity during AML progression, and identifies a relapse-enriched leukemic cell state with distinct transcriptional properties.
BLOOD CANCER DISCOVERY
(2022)