Article
Biochemical Research Methods
Yi Wang, Stephanie C. Hicks, Kasper D. Hansen
Summary: Estimates of correlation between genes in co-expression analysis are commonly used to construct gene networks. However, the distribution of these correlations depends on the observed expression level, resulting in a higher correlation for highly expressed genes. This relationship is not observed in protein-protein interaction data, indicating that it is not biologically relevant. To address this issue, we propose a method called spatial quantile normalization (SpQN) that normalizes local distributions in a correlation matrix, removing the mean-correlation relationship and correcting expression bias in network reconstruction.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Pierre-Aurelien Gilliot, Thomas E. Gorochowski
Summary: This article develops a Python package called FORECAST that accurately simulates cell-sorting and sequencing-based MPRAs and performs robust inference of genetic design function from MPRA data. The capabilities of FORECAST reveal rules for accurate genotype-to-phenotype links in MPRA experimental design and demonstrate how simulation of MPRA experiments can improve prediction accuracy when training deep learning-based classifiers. As MPRAs continue to grow in scale and scope, tools like FORECAST will help inform decision-making during their development and maximize the utility of the data produced.
Article
Biochemistry & Molecular Biology
Sue A. Krause, Gayle Overend, Julian A. T. Dow, David P. Leader
Summary: FlyAtlas 2 is a database and web application for studying gene expression in different tissues of Drosophila melanogaster, with enhancements including a 'Profile' search function and a dedicated feature for exploring gene expression in the larval midgut. The database now includes data from 13 tissues, five sex-specific tissues, and eight larval tissues, with major improvements to the interface.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Mengting Huang, Yixuan Yang, Xingzhao Wen, Weiqiang Xu, Na Lu, Xiao Sun, Jing Tu, Zuhong Lu
Summary: Although single cell RNA sequencing technologies are well developed, acquiring large-scale single cell expression data can still be costly. The study proposes a method of compressing expression profiles from the sample dimension by assigning each cell into multiple pools and demonstrates that expression profiles can be inferred from pool expression data with a overlapping pooling design and compressed sensing strategy. This approach, when combined with plate-based scRNA-seq measurement, maintains superior gene detection sensitivity and individual identity while reducing library costs by half.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Amichay Afriat, Vanessa Zuzarte-Luis, Keren Bahar Halpern, Lisa Buchauer, Sofia Marques, Angelo Ferreira Chora, Aparajita Lahree, Ido Amit, Maria M. Mota, Shalev Itzkovitz
Summary: This study characterized the temporal expression programs of the rodent malaria parasite Plasmodium berghei ANKA and the host hepatocyte in a zonally controlled manner using single-cell RNA sequencing and single-molecule transcript imaging. The study identified differences in parasite gene expression in distinct zones and identified a subpopulation of hepatocytes with reduced levels of Plasmodium transcripts and parasitophorous vacuole breakdown. These findings provide insights into the liver stage of Plasmodium infection.
Article
Biotechnology & Applied Microbiology
Jie Li, Kaihui Xie, Jiaojiao Yang, Juanli Zhang, Qiaoli Yang, Pengfei Wang, Shuangbao Gun, Xiaoyu Huang
Summary: This study identified downstream target genes regulated by S100A9 in Clostridium perfringens beta2 (CPB2) toxin-induced IPEC-J2 cell injury using RNA-Seq technique. The results showed that S100A9 was involved in CPB2-induced inflammatory response by regulating the expression of downstream target genes, promoting apoptosis, and aggravating oxidative cell damage. This study laid the foundation for further understanding the regulatory mechanism underlying piglet diarrhea.
Article
Biology
Ana Gutierrez-Franco, Franz Ake, Mohamed N. Hassan, Natalie Chaves Cayuela, Loris Mularoni, Mireya Plass
Summary: The critical step in single-cell transcriptomics is sample preparation. Different preservation methods show varying effects on cell quality and expression biases. In this study, methanol fixation is identified as the preferred method for droplet-based single-cell transcriptomics experiments on neural cell populations derived from induced pluripotent stem cells.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaonan Fu, Li Sun, Runze Dong, Jane Y. Chen, Runglawan Silakit, Logan F. Condon, Yiing Lin, Shin Lin, Richard D. Palmiter, Liangcai Gu
Summary: This study introduces a stamping method for fabricating polony gels, reducing the cost and time of barcode sequencing, and developing a single-cell spatial transcriptomic assay. This method offers high resolution and RNA capture efficiency for mapping and analyzing cell-cell communication in tissues.
Article
Multidisciplinary Sciences
Fengqin Guo, Yanliang Liu, Yanxiang Cheng, Qifan Zhang, Weili Quan, Yaxun Wei, Li Hong
Summary: This study found that FSCN1 is not only an actin-binding protein but also a transcriptional regulator and an angiogenic factor in cervical cancer. Knockdown of FSCN1 affects the transcription level of genes and the expression of genes in tumor-related pathways.
Article
Multidisciplinary Sciences
Asia Mendelevich, Svetlana Vinogradova, Saumya Gupta, Andrey A. Mironov, Shamil R. Sunyaev, Alexander A. Gimelbrant
Summary: The study demonstrates that relying on a single RNA-seq library for allele-specific analysis can lead to variable error rates. Therefore, the development of a computational tool like Qllelic, which accurately accounts for technical noise by utilizing replicate RNA-seq libraries, greatly decreases false positive rates and improves reproducibility of AI estimates.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
S. Kalra, R. Peyser, J. Ho, C. Babbin, N. Bohan, A. Cortes, J. Erley, M. Fatima, J. Flinn, E. Horwitz, R. Hsu, W. Lee, V. Lu, A. Narch, D. Navas, I. Kalu, E. Ouanemalay, S. Ross, F. Sowole, E. Specht, J. Woo, K. Yu, J. D. Coolon
Summary: Precise regulation of transcription is crucial for normal organism form and function, and minor alterations in gene expression can lead to phenotypic variation and disease. In this study, we investigated the response of target genes to systematic reduction of RAP1 expression in Saccharomyces cerevisiae. Our results revealed that Rap1 acts as an activator for more target genes than as a repressor and functions differently in different gene groups. These findings expand our understanding of this important transcriptional regulator.
Article
Multidisciplinary Sciences
Peijie Zhou, Shuxiong Wang, Tiejun Li, Qing Nie
Summary: MuTrans is a method based on multiscale reduction technique that can identify the underlying stochastic dynamics governing cell-fate transitions, construct cell-fate dynamical manifold, distinguish stable and transition cells, and quantify transition probabilities between cell states. The method is consistent with Langevin equation and transition rate theory, and has been shown to robustly unravel complex cell fate dynamics induced by transition cells in various systems. It bridges data-driven and model-based approaches for single-cell resolution analysis of cell-fate transitions.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Leo Machado, Frederic Relaix, Philippos Mourikis
Summary: The rapid advancement of single-cell RNA-sequencing technology has made it possible to generate comprehensive transcriptional maps of nearly all cells in multicellular tissues. Key elements such as scalability, spatial information, and accuracy of individual cell transcriptomes are critical in this process. Traditional cell-isolation protocols and new methods have been discussed in terms of capturing the transcriptional signatures of cells in their native tissue context, revealing new insights into biological processes.
TRENDS IN CELL BIOLOGY
(2021)
Article
Microbiology
Ileana D. Corsi, Soumita Dutta, Ambro van Hoof, Theresa M. Koehler
Summary: The study investigates the role of the sRNAs XrrA and XrrB encoded by the virulence plasmid pXO1 of Bacillus anthracis in regulating gene expression associated with branched-chain amino acid metabolism, proteolysis, and transmembrane transport. The sRNAs are highly stable primary transcripts whose expression is dependent upon the master virulence regulator AtxA. XrrA appears to have a greater regulatory effect compared to XrrB, with both sRNAs showing potential functional overlap. In a mouse model for systemic anthrax, the lungs and livers of animals infected with xrrA-null mutants exhibited a slight reduction in bacterial burden, suggesting a role for XrrA in B. anthracis pathogenesis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Andres R. Munoz-Rojas, Ilana Kelsey, Jenna L. Pappalardo, Meibin Chen, Kathryn Miller-Jensen
Summary: The study using single-cell RNA sequencing to explore co-stimulated macrophages reveals cell-to-cell heterogeneity in transcription and mutually exclusive expression of specific genes, supporting the maintenance of specialized functions for at least 48 hours. This suggests that increasing functional diversity in the macrophage population is an effective strategy to respond to conflicting environmental cues.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Priyangi A. Alwis, Puthayalai Treerat, Lan Gong, Deanna Deveson Lucas, Elizabeth M. Allwood, Mark Prescott, Rodney J. Devenish, Ben Adler, John D. Boyce
VETERINARY MICROBIOLOGY
(2020)
Article
Infectious Diseases
Nusaibah Abdul Rahim, Soon-Ee Cheah, Matthew D. Johnson, Yan Zhu, Heidi H. Yu, Hanna E. Sidjabat, Mark S. Butler, Matthew A. Cooper, Jing Fu, David L. Paterson, Roger L. Nation, John D. Boyce, Phillip J. Bergen, Tony Velkov, Jian Li
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2020)
Article
Chemistry, Multidisciplinary
Yan Zhu, Jing Lu, Mei-Ling Han, Xukai Jiang, Mohammad A. K. Azad, Nitin A. Patil, Yu-Wei Lin, Jinxin Zhao, Yang Hu, Heidi H. Yu, Ke Chen, John D. Boyce, Rhys A. Dunstan, Trevor Lithgow, Christopher K. Barlow, Weifeng Li, Elena K. Schneider-Futschik, Jiping Wang, Bin Gong, Bjorn Sommer, Darren J. Creek, Jing Fu, Lushan Wang, Falk Schreiber, Tony Velkov, Jian Li
Review
Pharmacology & Pharmacy
Yinzhi Lang, Nirav R. Shah, Xun Tao, Stephanie M. Reeve, Jieqiang Zhou, Bartolome Moya, Alaa R. M. Sayed, Suresh Dharuman, Jeremiah L. Oyer, Alicja J. Copik, Brett A. Fleischer, Eunjeong Shin, Carolin Werkman, Kari B. Basso, Deanna Deveson Lucas, Dhruvitkumar S. Sutaria, Marianne Megroz, Tae Hwan Kim, Victoria Loudon-Hossler, Amy Wright, Rossie H. Jimenez-Nieves, Miranda J. Wallace, Keisha C. Cadet, Yuanyuan Jiao, John D. Boyce, Eric D. LoVullo, Herbert P. Schweizer, Robert A. Bonomo, Nagakumar Bharatham, Brian T. Tsuji, Cornelia B. Landersdorfer, Michael H. Norris, Beom Soo Shin, Arnold Louie, Venkataraman Balasubramanian, Richard E. Lee, George L. Drusano, Juergen B. Bulitta
Summary: Multidrug-resistant bacteria pose a serious global health crisis, with a decline in antibiotic discovery and development investment hindering the adoption of new technologies. Novel mechanistic insights and translational strategies are needed to optimize patient therapy, particularly due to limited understanding of outer membrane permeability in Gram-negative bacteria. Developing a platform using the latest technologies to characterize target site penetration and receptor binding in intact bacteria is crucial for informing translational modeling and guiding new discoveries.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Biochemistry & Molecular Biology
Nitika Kandhari, Calvin A. Kraupner-Taylor, Paul F. Harrison, David R. Powell, Traude H. Beilharz
Summary: Alternative transcript cleavage and polyadenylation are associated with cancer cell transformation, proliferation, and outcome. Researchers have developed methods to detect and analyze alternative polyadenylation as potential cancer biomarkers, which, if integrated into standard prognostic measures, may advance cancer prognostic testing and guide therapy. This review focuses on existing methodologies, both experimental and computational, to support the use of alternative polyadenylation as cancer biomarkers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Nusaibah Abdul Rahim, Yan Zhu, Soon-Ee Cheah, Matthew D. Johnson, Heidi H. Yu, Hanna E. Sidjabat, Mark S. Butler, Matthew A. Cooper, Jing Fu, David L. Paterson, Roger L. Nation, John D. Boyce, Darren J. Creek, Phillip J. Bergen, Tony Velkov, Jian Li
Summary: Carbapenem-resistant Klebsiella pneumoniae is classified as an Urgent Threat by the CDC, while the combination of polymyxin and chloramphenicol has a synergistic killing effect against NDM-producing K. pneumoniae. Metabolomic and GSMN modeling results highlight the potential significance of this synergistic mechanism in developing precision antimicrobial chemotherapy in patients.
ACS INFECTIOUS DISEASES
(2021)
Article
Biology
Rachael Emily Turner, Paul F. Harrison, Angavai Swaminathan, Calvin A. Kraupner-Taylor, Belinda J. Goldie, Michael See, Amanda L. Peterson, Ralf B. Schittenhelm, David R. Powell, Darren J. Creek, Bernhard Dichtl, Traude H. Beilharz
Summary: This study investigates the regulation of mRNA function by 3' end formation factors, revealing that different drugs can impact the selection of poly(A) addition sites by influencing nucleotide levels and chromatin landscape to regulate alternative polyadenylation.
Article
Infectious Diseases
Jessica R. Tait, Hajira Bilal, Tae Hwan Kim, Abigail Oh, Anton Y. Peleg, John D. Boyce, Antonio Oliver, Phillip J. Bergen, Roger L. Nation, Cornelia B. Landersdorfer
Summary: The study showed that the combination of ceftazidime and tobramycin has a good bactericidal effect and can suppress resistance in hypermutable Pseudomonas aeruginosa strains. In vitro experiments simulating treatment regimens revealed that high-dose combination therapy is more effective against susceptible strains.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2021)
Article
Microbiology
Sebastien Massier, Brandon Robin, Marianne Megroz, Amy Wright, Marina Harper, Brooke Hayes, Pascal Cosette, Isabelle Broutin, John D. Boyce, Emmanuelle De, Julie Hardouin
Summary: Acinetobacter baumannii is a problematic nosocomial pathogen due to its antibiotic resistance and ability to form biofilms. The study identified phosphoproteins in two strains cultured in different growth modes, with biofilm modes showing more phosphorylation sites and proteins. The research suggests potential therapeutic targets against this pathogen.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Emily L. Gulliver, Brandon M. Sy, Julia L. Wong, Deanna S. Deveson Lucas, David R. Powell, Marina Harper, Jai J. Tree, John D. Boyce
Summary: Regulation in P. multocida involving the RNA-binding protein Hfq is required for hyaluronic acid capsule production and virulence. This study further expands our understanding of riboregulation by examining the role of a second RNA-binding protein, ProQ, in transcript regulation and abundance in P. multocida. The analyses demonstrated that ProQ binds to specific RNA targets and stabilizes sRNAs and transfer RNAs in P. multocida.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Microbiology
Thomas R. Smallman, Galain C. Williams, Marina Harper, John D. Boyce
Summary: This study identified essential genes for in vitro growth of P. multocida and genes required for hyaluronic acid capsule production and regulation using transposon-directed insertion site sequencing (TraDIS) and TraDISort. It found that many capsule-associated genes were involved in the stringent response, and disruption of the autoregulatory domains in SpoT resulted in reduced capsule biosynthesis and an acapsular phenotype.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Claudia Simm, Harshini Weerasinghe, David R. Thomas, Paul F. Harrison, Hayley J. Newton, Traude H. Beilharz, Ana Traven
Summary: Fungal infections, particularly drug-resistant ones like Candida auris, pose a global threat. However, the limited number of antifungal drug targets hinders effective treatment. This study investigates the metabolic requirements and adaptations of C. auris. The researchers find that triggering metabolic dysfunction using pyrvinium pamoate (PP) shows promise as a strategy against C. auris. PP induces metabolic reprogramming, disrupts mitochondrial function, and impairs iron homeostasis, leading to a reduction in C. auris growth. This study highlights the potential of targeting metabolism as a therapeutic approach for drug-resistant C. auris.
MICROBIOLOGY SPECTRUM
(2022)
Article
Computer Science, Interdisciplinary Applications
Paul Harrison
Summary: langevitour is a tool that displays interactive animated 2D projections of high-dimensional datasets. It uses Langevin Dynamics to generate a smooth path of projections, initially explored at random. Users can activate a guide to search for informative projections or manually adjust the position of variables. By providing continuous small motions, langevitour offers a channel of visual information that is not present in static scatter plots. Implemented in Javascript, it ensures a high frame rate and responsive interaction, and can be used directly from the R environment.
Article
Biochemistry & Molecular Biology
Frank St Michael, Chantelle M. Cairns, Perry Fleming, Evgeny V. Vinogradov, John D. Boyce, Marina Harper, Andrew D. Cox
Summary: The study focused on characterizing the structural features of capsular polysaccharides (CPSs) of Pasteurella multocida serotypes B and E. Through structural analysis and development of polyclonal sera, significant similarities and differences were identified between the two serotypes, shedding light on the genetic loci and roles of encoded proteins in CPS biosynthesis.
Article
Biochemistry & Molecular Biology
Mengyao Li, Su Mon Aye, Maizbha Uddin Ahmed, Mei-Ling Han, Chen Li, Jiangning Song, John D. Boyce, David R. Powell, Mohammad A. K. Azad, Tony Velkov, Yan Zhu, Jian Li