Article
Biochemistry & Molecular Biology
Keyi Geng, Lara G. Merino, Linda Wedemann, Aniek Martens, Malgorzata Sobota, Yerma P. Sanchez, Jonas Norskov Sondergaard, Robert J. White, Claudia Kutter
Summary: This study investigates the genomic rearrangements induced by the CRISPR-Cas9 system using an innovative droplet-based target enrichment approach and long-read sequencing. The researchers found extensive genomic disruptions, including genomic duplications, inversions of the target region, integrations of exogenous DNA, and rearrangements of interchromosomal DNA fragments. Furthermore, these genomic alterations were found to lead to functional aberrant DNA fragments and alter cell proliferation. The findings broaden our understanding of the consequences of the Cas9 deletion system and emphasize the importance of meticulous genomic validations.
Article
Oncology
Marcel da Camara Ribeiro-Dantas, Danilo Oliveira Imparato, Matheus Gibeke Siqueira Dalmolin, Caroline Brunetto de Farias, Andre Tesainer Brunetto, Mariane da Cunha Jaeger, Rafael Roesler, Marialva Sinigaglia, Rodrigo Juliani Siqueira Dalmolin
Summary: Ewing Sarcoma is a rare cancer with significant impact on patient prognosis. By inferring gene regulatory networks, potential master regulators can be identified to predict patient outcomes. This study sheds light on understanding the regulatory mechanisms and potential prognostic factors of Ewing Sarcoma.
Article
Dentistry, Oral Surgery & Medicine
Y. Chiba, K. Yoshizaki, T. Tian, K. Miyazaki, D. Martin, K. Saito, A. Yamada, S. Fukumoto
Summary: This study identifies important genes involved in tooth development by combining scRNA-seq and CAGE-seq, revealing novel features of the gene expression profile in dental cells and determining tooth-enriched and cell type-specific marker genes. The integration of scRNA-seq and CAGE-seq highlights key genes for tooth development among diverse gene expression profiles, contributing to understanding the mechanism of tooth development and laying the foundation for tooth regeneration in the future.
JOURNAL OF DENTAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Mallory J. DiVincenzo, Colin D. Angell, Lorena P. Suarez-Kelly, Casey Ren, Zoe Barricklow, Maribelle Moufawad, Paolo Fadda, Lianbo Yu, Floor J. Backes, Kari Ring, Anne Mills, Craig Slingluff, Catherine Chung, Alejandro A. Gru, William E. E. Carson III
Summary: This study investigates the expression profiles of microRNAs (miRNAs) and messenger RNAs (mRNAs) in melanomas from gynecologic sites (MOGS) and identifies specific dysregulation patterns. The findings suggest that miRNAs play a role in mediating gene expression in MOGS and reveal potential therapeutic targets.
Article
Microbiology
Devon M. Fitzgerald, Anne M. Stringer, Carol Smith, Pascal Lapierre, Joseph T. Wade
Summary: Genome-scale analyses have found that many transcription factor binding sites are located within genes rather than upstream, but their function remains unclear. In this study, we examined the regulon of the transcription factor PhoB in Escherichia coli and found that the majority of PhoB binding sites are within genes. Surprisingly, these intragenic sites do not regulate transcription and are not conserved evolutionarily, suggesting that they may be genomic noise.
Article
Immunology
Daniel Crespo-Piazuelo, Yuliaxis Ramayo-Caldas, Olga Gonzalez-Rodriguez, Mariam Pascual, Raquel Quintanilla, Maria Ballester
Summary: Recent years have seen an increase in awareness of antimicrobial resistance and a societal demand for healthier meat products, leading to a focus on health-related traits in livestock production. Despite the genetic component of health- and immunity-related traits, their complex nature may require alternative approaches for analysis. Using the association weight matrix (AWM) approach, this study aimed to identify gene networks, key regulators, and candidate genes associated with immunocompetence in pigs by integrating multiple health-related traits. The results revealed new regulators associated with health-related traits in pigs and identified gene-by-gene interactions and candidate genes involved in pathways related to cell fate, metabolism, and immune functions.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
P. Andrew Chong, Michael L. Nosella, Manasvi Vanama, Roxana Ruiz-Arduengo, Julie D. Forman-Kay
Summary: O-GlcNAc transferase (OGT) is an essential enzyme that adds N-acetylglucosamine to proteins. Predicting glycosylation sites has been challenging due to the lack of experimentally verified sequences. This study identifies a set of sequences that are not glycosylated by OGT and demonstrates a compositional bias for OGT targets. The results also reveal that OGT's tetratricopeptide repeat region recognizes and promotes glycosylation of disordered protein segments.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Friederike A. Sandbaumhuter, Mariya Nezhyva, Per E. Andren, Erik T. Jansson
Summary: Thermal proteome profiling with ion-mobility-enhanced LC-MS provides versatile data sets for studying protein differential expression, thermal stability, and transcription factor activities. This study developed a multidimensional data analysis workflow to analyze the signaling processes downstream of MC3R activation and infer transcription factor activities. The results revealed altered thermal stability of 298 proteins and identified several transcription factors involved in the MC3R signaling cascade.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Anupam Mondal, Anatoly B. Kolomeisky
Summary: Associations of transcription factors (TFs) with specific sites on DNA initiate major cellular processes. The presence of nucleosomes on DNA in eukaryotic cells prevents TFs from binding, but nucleosome sliding and breathing can affect the target search dynamics of TFs. Through a theoretical framework and analysis of a stochastic model, it is found that pioneer TFs, which can invade nucleosomal DNA, locate specific sites faster for short sliding lengths, while normal TFs are faster for long sliding lengths. Nucleosome breathing has a stronger effect on protein search dynamics than nucleosome sliding.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Gary Napier, Susana Campino, Jody E. Phelan, Taane G. Clark
Summary: Using whole genome sequencing, we identified putative resistance markers for INH that can be used for genotypic drug-resistance profiling, aiding in the clinical management of tuberculosis.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Julia Sieber-Frank, Hans-Jurgen Stark, Simon Kalteis, Elena-Sophie Prigge, Richard Koehler, Carolin Andresen, Thomas Henkel, Georg Casari, Tobias Schubert, Wolfgang Fischl, Min Li-Weber, Peter H. Krammer, Magnus von Knebel Doeberitz, Juergen Kopitz, Matthias Kloor, Aysel Ahadova
Summary: Synthetic rocaglates show enhanced growth-inhibitory effects when combined with glucose anti-metabolite 2DG in various cancer cell lines, potentially by reducing glucose uptake through downregulation or abrogation of GLUT-1 expression. They regulate key pathways, such as glycolysis, differently in sensitive and resistant cells, demonstrating a selective effect on tumor cells.
Article
Microbiology
Jordan J. Aoyama, Medha Raina, Gisela Storz
Summary: This study constructs synthetic dual-function RNAs and investigates the functional organization of these RNAs. It provides insights into the features of natural and synthetic dual-function RNAs, with the goal of designing synthetic molecules for maximum regulatory impact.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Huifen Cao, Yufei Zhang, Ye Cai, Lu Tang, Fan Gao, Dongyang Xu, Philipp Kapranov
Summary: Single-strand breaks (SSBs) are a common type of DNA damage, and this study found that they exhibit hotspot characteristics in the human genome, with a prominent enrichment near transcriptional start sites (TSSs). These TSS-associated hotspots may be generated by a novel mechanism involving preferential cleavage at specific sites. These findings support recent studies suggesting a complex relationship between DNA damage and gene expression regulation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Meropi Bagka, Hyeonyi Choi, Margaux Heritier, Hanna Schwaemmle, Quentin T. L. Pasquer, Simon M. G. Braun, Leonardo Scapozza, Yibo Wu, Sascha Hoogendoorn
Summary: This study reveals that the cellular target of Hedgehog Pathway Inhibitor-1 is BET bromodomains by converting it into a bifunctional degrader. The strategy combines PROTACs and label-free quantitative proteomics to identify and validate the target, providing an effective approach for target deconvolution from phenotypic screens.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
David J. Birnbaum, Sebastian K. S. Begg, Pascal Finetti, Charles Vanderburg, Anupriya S. Kulkarni, Azfar Neyaz, Thomas Hank, Eric Tai, Vikram Deshpande, Francois Bertucci, Daniel Birnbaum, Keith D. Lillemoe, Andrew L. Warshaw, Mari Mino-Kenudson, Carlos Fernandez-Del Castillo, David T. Ting, Andrew S. Liss
Summary: This study identified specific molecular subtypes of PDAC through laser capture microdissection, and found gene expression signatures associated with short-term and long-term survival. These findings provide new insights into predicting patient survival based on the cancer- and stroma-specific features of PDAC.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Georgina D. Barnabas, Joo Sang Lee, Tamar Shami, Michal Harel, Lir Beck, Michael Selitrennik, Livnat Jerby-Arnon, Neta Erez, Eytan Ruppin, Tamar Geiger
Summary: This study highlights the crucial role of IDH2 in triple-negative breast cancer (TNBC) and HER2, and demonstrates its oncogenic effects in cell proliferation, glycolysis, and other metabolic processes. PHGDH and PSAT1 are identified as synthetic dosage lethal (SDL) partners of IDH2, and their knockout shows the essentiality in IDH2-high cells. Clinical findings suggest that patients with IDH2-high/PHGDH-low tumors have longer survival, and PHGDH inhibitors show effectiveness in treating IDH2-high cells.
Correction
Genetics & Heredity
Erez Persi, Yuri I. Wolf, David Horn, Eytan Ruppin, Francesca Demichelis, Robert A. Gatenby, Robert J. Gillies, Eugene V. Koonin
NATURE REVIEWS GENETICS
(2021)
Review
Genetics & Heredity
Erez Persi, Yuri Wolf, David Horn, Eytan Ruppin, Francesca Demichelis, Robert A. Gatenby, Robert J. Gillies, Eugene Koonin
Summary: Intratumour heterogeneity and phenotypic plasticity enabled by various somatic aberrations, epigenetic and metabolic adaptations, play a crucial role in helping cancers resist treatment and survive under environmental stress. Understanding the interplay between genetic aberrations, the microenvironment, and epigenetic and metabolic cellular states is essential for early detection, prevention, and development of efficient therapeutic strategies for cancer.
NATURE REVIEWS GENETICS
(2021)
Article
Multidisciplinary Sciences
Kuoyuan Cheng, Nishanth Ulhas Nair, Joo Sang Lee, Eytan Ruppin
Summary: This study investigates the role of synthetic lethality in cancer risk, finding that the extent of co-inactivation of cancer synthetic lethal (cSL) gene pairs in normal tissues is associated with lower and delayed cancer risk. The up-regulation of more cSL gene pairs in cells exposed to carcinogens and in premalignant stages suggests a potential role of synthetic lethality in tumorigenesis. Moreover, the tissue specificity of tumor suppressor genes is linked to the expression of their cSL partner genes in normal tissues.
Article
Multidisciplinary Sciences
Mahashweta Basu, Kun Wang, Eytan Ruppin, Sridhar Hannenhalli
Summary: This study demonstrates that an individual's whole blood transcriptome can predict tissue-specific expression levels for around 60% of genes across various tissues, with particularly high accuracy in skeletal muscle. Predictions based on blood transcriptome are almost as effective as actual tissue expression in identifying disease states for six different complex disorders, surpassing the traditional blood transcriptome approach. The development of TEEBoT provides a valuable tool for further research in other medical conditions.
Article
Oncology
Vishaka Gopalan, Arashdeep Singh, Farid Rashidi Mehrabadi, Li Wang, Eytan Ruppin, H. Efsun Arda, Sridhar Hannenhalli
Summary: This study identifies edge epithelial cell states with oncogenic transcriptional activity in human organs without oncogenic mutations, with a particular focus on pancreatic ductal adenocarcinoma (PDAC). It also highlights the increase in the fraction of acinar cells with age in the pancreas, as well as the significantly higher presence of AE-like cells in human pancreatitis samples.
Article
Biology
Ariel Israel, Alejandro A. Schaffer, Assi Cicurel, Kuoyuan Cheng, Sanju Sinha, Eyal Schiff, Ilan Feldhamer, Ameer Tal, Gil Lavie, Eytan Ruppin
Summary: This study aimed to investigate the impact of existing medications on the risk of severe COVID-19 hospitalization and found that several medications, including ubiquinone, ezetimibe, rosuvastatin, flecainide, and vitamin D, were associated with reduced risk of hospitalization. These findings suggest a promising protective effect that warrants further investigation in prospective studies.
Article
Biochemistry & Molecular Biology
Kuoyuan Cheng, Laura Martin-Sancho, Lipika R. Pal, Yuan Pu, Laura Riva, Xin Yin, Sanju Sinha, Nishanth Ulhas Nair, Sumit K. Chanda, Eytan Ruppin
Summary: The study utilized genome-scale metabolic modeling to analyze host metabolism changes during SARS-CoV-2 infection, predicted anti-viral targets, validated these targets using drug and genetic screening data, and provided potential anti-SARS-CoV-2 targets supported by clinical data for future evaluation.
MOLECULAR SYSTEMS BIOLOGY
(2021)
Article
Oncology
Kun Wang, Sushant Patkar, Joo Sang Lee, E. Michael Gertz, Welles Robinson, Fiorella Schischlik, David R. Crawford, Alejandro A. Schaeffer, Eytan Ruppin
Summary: This study presents two new computational methods that deconvolve tumor gene expression profiles and predict response to immune checkpoint blockade therapy.
Article
Medicine, General & Internal
Ariel Israel, Eugene Merzon, Alejandro A. Schaffer, Yotam Shenhar, Ilan Green, Avivit Golan-Cohen, Eytan Ruppin, Eli Magen, Shlomo Vinker
Summary: In this study, it was found that the risk of COVID-19 infection gradually increased in adults who received their second dose of the BNT162b2 mRNA vaccine after at least 90 days, based on electronic health records.
BMJ-BRITISH MEDICAL JOURNAL
(2021)
Article
Immunology
Ariel Israel, Yotam Shenhar, Ilan Green, Eugene Merzon, Avivit Golan-Cohen, Alejandro A. Schaeffer, Eytan Ruppin, Shlomo Vinker, Eli Magen
Summary: This study demonstrates that individuals who received the Pfizer-BioNTech mRNA vaccine have higher initial levels of antibodies compared to patients who had been infected with the SARS-CoV-2 virus, but experience a much faster exponential decrease in antibody levels.
Article
Oncology
Marzia Scortegagna, Yuanning Du, Linda M. Bradley, Kun Wang, Alfredo Molinolo, Eytan Ruppin, Rabi Murad, Ze'ev A. Ronai
Summary: Cellular components, such as myeloid cells, in the tumor microenvironment have significant impact on the progression and treatment response of lung adenocarcinoma (LUAD). This study reveals that the ubiquitin ligases Siah1a/2 regulate the differentiation and activity of alveolar macrophages (AM), and their control of AMs influences carcinogen-induced LUAD. The findings indicate that Siah1a/2 in AMs act as gatekeepers of lung cancer development by controlling inflammatory signaling, differentiation, and profibrotic phenotypes.
Review
Oncology
Peng Jiang, Sanju Sinha, Kenneth Aldape, Sridhar Hannenhalli, Cenk Sahinalp, Eytan Ruppin
Summary: Historically, cancer research has focused on a few essential pathways and genes, but recent advances in high-throughput technologies have led to the rapid accumulation of large-scale cancer omics data. The analysis of this "big data" requires significant computational resources and has the potential to bring new insights to cancer research. The combination of big data, bioinformatics, and artificial intelligence has already made notable advances in our understanding of cancer biology and translational research. Future progress will require collaboration among data scientists, clinicians, biologists, and policymakers.
NATURE REVIEWS CANCER
(2022)
Article
Oncology
Neelam Sinha, Sanju Sinha, Cristina Valero, Alejandro A. Scha, Kenneth Aldape, Kevin Litch, Timothy A. Chan, Luc G. T. Morris, Eytan Ruppin
Summary: This study uncovers immune-related factors that may modulate the relationship between high tumor mutational burden and ICI response, which can help prioritize cancer types for clinical trials.
Meeting Abstract
Oncology
Xuan C. Li, Yuelin Liu, Farid Rashidi, Salem Malikic, Stephen M. Mount, Eytan Ruppin, Kenneth Aldape, Cenk Sahinalp