Article
Biochemistry & Molecular Biology
Aroa Rey Campa, Leah M. Smith, Hannah G. Hampton, Sahil Sharma, Simon A. Jackson, Thorsten Bischler, Cynthia M. Sharma, Peter C. Fineran
Summary: Studies have shown that the Rsm/Csr pathway plays a key role in regulating the expression of multiple CRISPR-Cas systems in Serratia, allowing modulation of adaptive immunity through coregulation of CRISPR-Cas and flagella.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Kaiyuan Wang, Mario Escobar, Jing Li, Barun Mahata, Jacob Goell, Spencer Shah, Madeleine Cluck, Isaac B. Hilton
Summary: This study systematically compared different dCas9-based transcriptional activators and found that their expression levels and transactivation efficacies vary in different human cell types. The study also showed that these activators can induce the production of enhancer RNAs, which are positively correlated with downstream mRNA expression. Additionally, the study demonstrated the existence of intrinsic transcriptional and epigenetic reciprocity between human enhancers and promoters.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Violaine Saint-Andre
Summary: The review discusses the main approaches and tools for mapping Transcriptional Regulatory Networks (TRNs) from high-throughput data, highlighting their advantages and limitations. It summarizes the main principles defining the topology and structure-function relationships in TRNs, and presents an overview of the work done to map TRNs from bulk transcriptomic data by methodological approach. Additionally, it touches upon recent modeling of TRNs using different types of molecular data and concludes with expected improvements in the field.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Carolina H. Chung, Da-Wei Lin, Alec Eames, Sriram Chandrasekaran
Summary: Genome-scale metabolic models are powerful for understanding metabolism but lack cellular regulation. Integrative models encompassing six types of regulatory mechanisms have been developed to enhance predictive capabilities, with 22 methods discussed for simulating metabolic regulation. Challenges remain in constructing GEMs with regulation, and next-generation integrative GEMs will be crucial for discovering cell-type and disease-specific metabolic control mechanisms.
Article
Genetics & Heredity
Christelle Adolphe, Angli Xue, Atefeh Taherian Fard, Laura A. Genovesi, Jian Yang, Brandon J. Wainwright
Summary: The study identified 71 BCC susceptibility loci and 46 functional candidate susceptibility genes through GWAS, indicating that increased risk of BCC is associated with decreased expression of some susceptibility genes and increased expression of others. Pathway analysis revealed enrichment of cell cycle, cell death, and immune regulation processes in BCC susceptibility, with genes linked to T-Reg cell biology showing global enrichment.
Article
Biochemical Research Methods
Eric Ching-Pan Chu, Alexander Morin, Tak Hou Calvin Chang, Tue Nguyen, Yi-Cheng Tsai, Aman Sharma, Chao Chun Liu, Paul Pavlidis
Summary: By curating published literature, a collection of 1499 unique direct transcriptional regulatory interactions (DTRIs) involving 251 transcription factors (TFs) and 825 target genes was assembled. The majority of DTRIs (64%) were supported by two or more types of experimental evidence, with 27% supported by all three types. This study demonstrates the potential of assembling a high resolution DTRI resource to support the development of large-scale transcriptional regulatory networks (TRNs).
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bjort K. Kragesteen, Amir Giladi, Eyal David, Shahar Halevi, Laufey Geirsdottir, Olga M. Lempke, Baoguo Li, Andreas M. Bapst, Ken Xie, Yonatan Katzenelenbogen, Sophie L. Dahl, Fadi Sheban, Anna Gurevich-Shapiro, Mor Zada, Truong San Phan, Roberto Avellino, Shuang-Yin Wang, Oren Barboy, Shir Shlomi-Loubaton, Sandra Winning, Philipp P. Markwerth, Snir Dekalo, Hadas Keren-Shaul, Merav Kedmi, Martin Sikora, Joachim Fandrey, Thorfinn S. Korneliussen, Josef T. Prchal, Barak Rosenzweig, Vladimir Yutkin, Fernando Racimo, Eske Willerslev, Chamutal Gur, Roland H. Wenger, Ido Amit
Summary: Single-cell RNA and transposase-accessible chromatin (ATAC) sequencing in a mouse model identified a rare cell subset called Norn cells in kidney stroma as the major source of endocrine Epo production in mice, and this finding was confirmed in human kidney tissues. These findings provide new insights into EPO gene regulation and may lead to improved therapies for anemia.
Article
Multidisciplinary Sciences
Hongxu Ding, Ying Yang, Yuanqing Xue, Lucas Seninge, Henry Gong, Rojin Safavi, Andrea Califano, Joshua M. Stuart
Summary: This study demonstrates that the dynamic changes of biological states are controlled by coordinated transcription factors within gene regulatory networks, and TFs responsible for these changes can be prioritized and extended through temporal PageRank and multiplex PageRank, integrating gene regulatory networks reverse engineered from multi-omics profiles.
Article
Biotechnology & Applied Microbiology
Abozar Ghorbani, Mahsa Rostami, Keramatollah Izadpanah
Summary: In this study, critical genes and key pathways involved in Maize Iranian mosaic virus (MIMV) infection were identified through transcriptome data analysis. The study also revealed the important role of the cellular endoplasmic reticulum in MIMV infection. The discovered miRNAs belonging to various families provide insights into pathogenicity and resistance processes against MIMV and other viruses.
Article
Multidisciplinary Sciences
Surama Biswas, Santosh Manicka, Erik Hoel, Michael Levin
Summary: Studies have shown that gene regulatory networks possess various types of memory, which is important for understanding the variability and time-dependent changes of drug action. Defining and identifying memory through a computational framework is beneficial for the biomedical field. Timed stimuli offer a powerful alternative for controlling complex in vivo dynamics.
Article
Biochemistry & Molecular Biology
Ekaterina Kotelnikova, Klaus M. Frahm, Dima L. Shepelyansky, Oksana Kunduzova
Summary: In this study, the MetaCore network and Google matrix algorithms were used to predict protein-protein interactions influencing cardiac fibrosis. The developed algorithms allowed for the identification of key protein interactions and prediction of new regulators linked to fibroblast activation. These findings are important for the discovery of new therapeutic targets to limit myocardial fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Computer Science, Artificial Intelligence
Shasha Xiao, Zhanshan Wang
Summary: This paper investigates the finite-time stability for delayed genetic regulatory networks with reaction-diffusion terms by proposing a linear parameterization method and establishing sufficient conditions through theoretical analysis. The simulation verifications indicate the validity of the theoretical results in ensuring the stability of the networks.
COMPLEX & INTELLIGENT SYSTEMS
(2022)
Article
Developmental Biology
Ha T. H. Vu, Regan L. Scott, Khursheed Iqbal, Michael J. Soares, Geetu Tuteja
Summary: In this study, the chromatin accessibility and gene regulation patterns of invasive trophoblast cells in rat and human were compared using single-nucleus ATAC-seq and single-cell RNA-seq data. Similarities in gene regulation and enriched motifs were found between the two species, and a conserved gene regulatory network in invasive trophoblast cells was identified.
Article
Multidisciplinary Sciences
Mike Thompson, Mary Grace Gordon, Andrew Lu, Anchit Tandon, Eran Halperin, Alexander Gusev, Chun Jimmie Ye, Brunilda Balliu, Noah Zaitlen
Summary: This study presents a method for transcriptome-wide association studies (TWAS) that considers the context-specific and context-shared effects of genetic variants. The authors demonstrate that their method improves the power of TWAS and identifies more genetically predicted genes associated with complex traits. The study highlights the importance of accounting for context-specific effects when analyzing transcriptome data.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Beatriz Andrea Otalora-Otalora, Cristian Gonzalez Prieto, Lucia Guerrero, Camila Bernal-Forigua, Martin Montecino, Alejandra Canas, Liliana Lopez-Kleine, Adriana Rojas
Summary: The use of a new bioinformatics pipeline identified deregulated transcription factors in lung cancer, with RUNX2 potentially playing a key role in the gene regulatory network. Experimental validation of RUNX2's regulatory function could lead to its use as a biomarker for diagnostic tools and specific treatments against lung tumoral diseases.
Article
Psychology, Biological
Yaqiong Xiao, Teresa H. Wen, Lauren Kupis, Lisa T. Eyler, Disha Goel, Keith Vaux, Michael Lombardo, Nathan E. Lewis, Karen Pierce, Eric Courchesne
Summary: Motherese, or affective speech, plays a crucial role in the development of infants, but toddlers with autism show reduced preference for motherese and impaired brain responses to it.
NATURE HUMAN BEHAVIOUR
(2022)
Article
Biotechnology & Applied Microbiology
Bryan E. Thacker, Kristen J. Thorne, Colin Cartwright, Jeeyoung Park, Kimberly Glass, Annie Chea, Benjamin P. Kellman, Nathan E. Lewis, Zhenping Wang, Anna Di Nardo, Susan T. Sharfstein, Walter Jeske, Jeanine Walenga, John Hogwood, Elaine Gray, Barbara Mulloy, Jeffrey D. Esko, Charles A. Glass
Summary: Heparin, an essential anticoagulant, is currently sourced from vulnerable animal populations. This study demonstrates the feasibility of producing high anticoagulant potency heparin sulfate through genome engineering in cell culture, providing a potential alternative to animal sources.
METABOLIC ENGINEERING
(2022)
Correction
Biochemistry & Molecular Biology
Ryan J. Weiss, Philipp N. Spahn, Austin W. T. Chiang, Qing Liu, Jing Li, Kristina M. Hamill, Sandra Rother, Thomas M. Clausen, Marten A. Hoeksema, Bryce M. Timm, Kamil Godula, Christopher K. Glass, Yitzhak Tor, Philip L. S. M. Gordts, Nathan E. Lewis, Jeffrey D. Esko
NATURE CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Benjamin P. Kellman, Anne Richelle, Jeong-Yeh Yang, Digantkumar Chapla, Austin W. T. Chiang, Julia Najera, Bokan Bao, Natalia Koga, Mahmoud A. Mohammad, Anders Bech Bruntse, Morey W. Haymond, Kelley W. Moremen, Lars Bode, Nathan E. Lewis, Chenguang Liang, Annalee Furst
Summary: This study constructs a biosynthetic network for Human Milk Oligosaccharides (HMOs) using a systems biology framework and predicts the involved glycosyltransferases. The research provides a molecular basis for HMO biosynthesis, guiding progress in understanding and improving infant health and development.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Chih-Ming Tsai, J. R. Caldera, Irshad A. Hajam, Austin W. T. Chiang, Chih-Hsiung Tsai, Haining Li, Maria Lazaro Diez, Cesia Gonzalez, Desmond Trieu, Gislaine A. Martins, David M. Underhill, Moshe Arditi, Nathan E. Lewis, George Y. Liu
Summary: Natural exposure to Staphylococcus aureus (SA) may explain the failure of anti-SA immunization trials. Animals infected with SA do not mount protective antibody responses to vaccination, unlike naive animals.
CELL HOST & MICROBE
(2022)
Article
Biotechnology & Applied Microbiology
Magdalena Malm, Chih-Chung Kuo, Mona Moradi Barzadd, Aman Mebrahtu, Num Wistbacka, Ronia Razavi, Anna-Luisa Volk, Magnus Lundqvist, David Kotol, Hanna Tegel, Sophia Hober, Fredrik Edfors, Torbjorn Graslund, Veronique Chotteau, Ray Field, Paul G. Varley, Robert G. Roth, Nathan E. Lewis, Diane Hatton, Johan Rockberg
Summary: This study identifies metabolic engineering targets limiting expression of recombinant human proteins, and demonstrates the improved secretion of challenging human proteins upon host cell swapping from CHO to HEK293. It also shows that the elevated activities of glycosyltransferases in HEK293 benefit heavily glycosylated products.
METABOLIC ENGINEERING
(2022)
Article
Multidisciplinary Sciences
Erick Armingol, Hratch M. Baghdassarian, Cameron Martino, Araceli Perez-Lopez, Caitlin Aamodt, Rob Knight, Nathan E. Lewis
Summary: In this study, the authors introduce a new method called Tensor-cell2cell for deciphering context-driven intercellular communication. By considering multiple stages, states, or locations of cells, Tensor-cell2cell can uncover communication patterns associated with different phenotypic states and provide the ability to identify communication modules related to disease severity.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Chintan J. Joshi, Wenfan Ke, Anna Drangowska-Way, Eyleen J. O'Rourke, Nathan E. Lewis
Summary: The concept of housekeeping gene, which is essential for cellular existence and stably expressed, remains loosely defined. This study presents a quantitative and experimentally supported definition of housekeeping genes by using genome-scale functional genomic screens and sequencing technologies. The authors identify and characterize housekeeping genes in multiple human datasets and other animal species, and find that the essential and stably expressed genes can vary across organisms while the enriched pathways are conserved. This research provides insights into the unique biological and evolutionary characteristics of housekeeping genes.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Microbiology
James T. Sorrentino, Gregory J. Golden, Claire Morris, Chelsea D. Painter, Victor Nizet, Alexandre Rosa Campos, Jeffrey W. Smith, Christofer Karlsson, Johan Malmstrom, Nathan E. Lewis, Jeffrey D. Esko, Alejandro Gomez Toledo
Summary: Studies have found that sepsis can cause specific alterations in the cellular proteome of organs, and these changes are closely related to disease progression and organ failure. Dysregulated vascular responses may play a potential role in organ failure during sepsis.
Article
Biochemistry & Molecular Biology
Bokan Bao, Javad Zahiri, Vahid H. Gazestani, Linda Lopez, Yaqiong Xiao, Raphael Kim, Teresa H. Wen, Austin W. T. Chiang, Srinivasa Nalabolu, Karen Pierce, Kimberly Robasky, Tianyun Wang, Kendra Hoekzema, Evan E. Eichler, Nathan E. Lewis, Eric Courchesne
Summary: Autism Spectrum Disorder (ASD) diagnosis is currently behavior-based and lacks accurate early-age diagnostics. This study developed an ensemble classifier model using gene expression data, which can accurately diagnose ASD in toddlers. The performance of this model outperforms risk gene mutation-based diagnostic methods.
MOLECULAR PSYCHIATRY
(2023)
Article
Biotechnology & Applied Microbiology
Tae Kwang Ha, Andreu Odena, Karen Julie la Cour Karottki, Che Lin Kim, Hooman Hefzi, Gyun Min Lee, Helene Faustrup Kildegaard, Lars K. Nielsen, Lise Marie Grav, Nathan E. Lewis
Summary: The use of a dual selection method can greatly improve the efficiency of Chinese hamster ovary (CHO) cell lines in producing biotherapeutic proteins, although it may lead to reduced growth rate and viability. By knocking out the Gs/Aspg genes, a novel dual selectable system was successfully constructed, which showed significantly improved productivity and titer compared to the standard Gs system under the same selection conditions. With further optimization of culture medium and selection conditions, this approach is expected to be an effective addition to industrial workflows for producing recombinant biotherapeutics.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Saratram Gopalakrishnan, Chintan J. Joshi, Miguel A. Valderrama-Gomez, Elcin Icten, Pablo Rolandi, William Johnson, Cleo Kontoravdi, Nathan E. Lewis
Summary: Genome-scale metabolic models can be customized to simulate condition-specific physiology by using omics data. The choice of algorithm and the existence of alternate context-specific models can impact the quality of these models. In this study, various extraction methods were evaluated for microbial and mammalian model extraction, and it was found that protecting the metabolic tasks defining an organism's phenotype is crucial. The algorithm choice and the topological properties of the parent genome-scale model greatly influence the scope of alternate models. mCADRE generated the most reproducible context-specific models, while MBA had the most alternate solutions. GIMME performed well in E. coli, while mCADRE was better suited for complex mammalian models.
METABOLIC ENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Pavlos Kotidis, Roberto Donini, Johnny Arnsdorf, Anders Holmgaard Hansen, Bjorn Gunnar Rude Voldborg, Austin W. T. Chiang, Stuart M. Haslam, Michael Betenbaugh, Ioscani Jimenez del Val, Nathan E. Lewis, Frederick Krambeck, Cleo Kontoravdi
Summary: Researchers constructed a comprehensive glycosylation reaction network, CHOGlycoNET, based on 200 glycan datasets from CHO cell lines. They used machine learning and dimensionality reduction techniques to explore the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key reactions. CHOGlycoNET can accelerate glycomodel development and predict the effect of glycoengineering strategies.
METABOLIC ENGINEERING
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Yixuan Xie, Qiongyu Li, Siyu Chen, Winnie Chen, Arpana Vaniya, Tyler Kim, John W. Newman, Oliver Fiehn, Carlito Lebrilla, Nancy L. Keim, Nathan E. Lewis, Sridevi Krishnan
Article
Biochemistry & Molecular Biology
Aniruddha Sasmal, Naazneen Khan, Zahra Khedri, Benjamin P. Kellman, Saurabh Srivastava, Andrea Verhagen, Hai Yu, Anders Bech Bruntse, Sandra Diaz, Nissi Varki, Travis Beddoe, Adrienne W. Paton, James C. Paton, Xi Chen, Nathan E. Lewis, Ajit Varki
Summary: This study presents a simple encoding system for sialyltrisaccharides and utilizes sialoglycan microarray to compare the interactions between bacterial toxin B subunits and sialoglycans. The results reveal the enormous diversity of sialoglycans in structure and recognition preferences.