Article
Biochemistry & Molecular Biology
Andrea Ameruoso, Maria Claudia Villegas Kcam, Katherine Piper Cohen, James Chappell
Summary: The rise of antibiotic-resistant bacteria is a major threat to global health, necessitating the discovery of new antibiotics. Natural products derived from Streptomyces offer a diverse pool of chemical molecules for potential antibiotic discovery. However, the poor expression of biosynthetic gene clusters (BGCs) responsible for natural product synthesis under laboratory conditions poses a challenge for isolating and screening novel chemicals. This study presents a novel approach using synthetic gene regulators based on CRISPR-Cas to activate silent BGCs by rewiring endogenous regulation. These tools enable programmable activation of silent BGCs and advance the synthetic regulatory toolbox for Streptomyces, facilitating the discovery of new chemical compounds.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Yajunzi Wang, Jing Li, Daiyun Huang, Yang Hao, Bo Li, Kai Wang, Boya Chen, Ting Li, Xin Liu
Summary: The development of high-throughput omics technologies allows for the quantification of genes and gene products, and pathway enrichment analysis (PEA) provides a solution for extracting biological insights. Topology-based pathway analysis (TPA) methods utilize pathway topology and gene expression data to explore causal relationships. In this study, different BN reconstruction strategies were compared, and results showed varying pathway rankings due to different cyclic structure removal strategies. These findings offer a reference for selecting appropriate methods for data analysis tasks.
Article
Biochemical Research Methods
Meriem Mekedem, Patrice Ravel, Jacques Colinge
Summary: Advancements in high-throughput genomic technologies have enabled the acquisition of large perturbation data sets, allowing for the reverse engineering of gene regulatory networks in specific cell types. Modular response analysis (MRA) has proven to be a promising mathematical modeling method for such network inference tasks, showing superior performance compared to general-purpose mutual information-based algorithms on large systems. The study also introduces novel heuristics and parallelization techniques to further improve MRA's performance and scalability on extensive biological systems.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Gat Rauner, Dexter X. Jin, Daniel H. Miller, Todd M. Gierahn, Carman M. Li, Ethan S. Sokol, Yu-Xiong Feng, Robert A. Mathis, J. Christopher Love, Piyush B. Gupta, Charlotte Kuperwasser
Summary: Mammary morphogenesis is a complex process in which stem cells build a three-dimensional multi-lineage tissue structure, including ducts and lobules. This process is orchestrated by signals transmitted through collagen receptors, coordinating structural changes to form a complex ductal-lobular network.
NATURE COMMUNICATIONS
(2021)
Review
Biochemical Research Methods
Peter D. Karp, Peter E. Midford, Richard Billington, Anamika Kothari, Markus Krummenacker, Mario Latendresse, Wai Kit Ong, Pallavi Subhraveti, Ron Caspi, Carol Fulcher, Ingrid M. Keseler, Suzanne M. Paley
Summary: The development of Pathway Tools software enables researchers to construct biological knowledge resources more efficiently, develop metabolic flux models, and interpret high-throughput data using pathway information.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Biotechnology & Applied Microbiology
Bozhidar-Adrian Stefanov, Martin Fussenegger
Summary: Current clinical therapies for chronic diseases carry the risk of under or overdosing, leading to ineffective treatment or undesirable side effects. To provide personalized treatment, synthetic systems that can generate calibrated therapeutic responses are necessary. These closed-loop devices should incorporate sensors to track disease severity and evaluate treatment effectiveness, as well as components for bio computing and delivering appropriate therapeutic outputs.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Analytical
JingYang Niu, Wei Xu, DongMing Wei, Kun Qian, Qian Wang
Summary: By proposing a joint deep learning framework that integrates batch effect removal, classification, and downstream pathway activities, we have validated its effectiveness on metabolomics datasets, achieving higher diagnostic accuracy and notable improvement over other methods.
ANALYTICAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Siras Hakobyan, Ani Stepanyan, Lilit Nersisyan, Hans Binder, Arsen Arakelyan
Summary: The PSF toolkit is an integrated solution that combines pathway curation and topology-based analysis. It provides interactive and command-line tools for importing, correcting, and modifying pathways from diverse sources, and conducting detailed topology-based pathway signal flow analysis. It addresses the limitations of current topology-based pathway analysis methods and enhances the quality, flexibility, and accessibility of pathway analysis.
FRONTIERS IN GENETICS
(2023)
Article
Ecology
Mohammad H. Mirhakkak, Sascha Schaeuble, Tilman E. Klassert, Sascha Brunke, Philipp Brandt, Daniel Loos, Ruben Uribe, Felipe Senne de Oliveira Lino, Yueqiong Ni, Slavena Vylkova, Hortense Slevogt, Bernhard Hube, Glen J. Weiss, Morten O. A. Sommer, Gianni Panagiotou
Summary: The study reconstructed a metabolic model of Candida albicans to investigate bacterial-fungal metabolic interactions in the gut, predicting key gut bacterial species modulating C. albicans colonization levels. The findings were confirmed through metagenomic sequencing and fungal growth experiments, demonstrating the potential impact of gut microbiome on harmful levels of C. albicans.
Article
Cell Biology
Bingbing Wu, Yu Li, Nanfang Nie, Xilin Shen, Wei Jiang, Yanshan Liu, Lin Gong, Chengrui An, Kun Zhao, Xudong Yao, Chunhui Yuan, Jinghui Hu, Wei Zhao, Jianhua Qian, XiaoHui Zou
Summary: Our study characterized the cells of human uterus using single cell RNA-sequencing, revealing the cell heterogeneity and population architecture of uterine tissues during the menstrual cycle. We identified a subpopulation of SFRP4(+) stromal cells that play a role in the regeneration of endometrial epithelial cells and injury repair.
Article
Cell Biology
Chunmei Fan, Yanyan Zhao, Yangwu Chen, Tian Qin, Junxin Lin, Shan Han, Ruojin Yan, Tingyun Lei, Yuanhao Xie, Tingzhang Wang, Shen Gu, Hongwei Ouyang, Weiliang Shen, Zi Yin, Xiao Chen
Summary: This study reveals that post-natal days 7-14 are the crucial transitional stage for mouse tendon maturation, and identifies a nerve growth factor (NGF)-secreting Cd9(+) Cd271(+) tendon stem/progenitor cell population that promotes the conversion from neonate to adult tendon. Additionally, SHP2 signaling is discovered to be a regulator for tendon maturation.
Article
Biochemistry & Molecular Biology
Christopher Tadhg James Wall, Gregory Lefebvre, Sylviane Metairon, Patrick Descombes, Andreas Wiederkehr, Jaime Santo-Domingo
Summary: We studied the shared transcriptional responses to three different mitochondrial respiratory chain inhibitors in human primary skin fibroblasts, and found that genes involved in the mevalonate pathway were downregulated. This pathway was also affected by impaired mitochondrial respiration at any of the three affected complexes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Jiaojiao Li, Peixian Li, Qian Liu, Jinjin Li, Hao Qi
Summary: Strict control of protein synthesis is crucial in synthetic biology. In this study, the consistency of 5'-UTR function in different bacterial cells and in vitro systems was systematically evaluated. The results showed a divergence between in vivo and in vitro protein translation, contrary to the strong correlation between two cellular systems. It was also found that the absence of nucleotide C and complex secondary structure in the 5'-UTR significantly improved protein translation efficiency.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
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)
Review
Genetics & Heredity
Kangmei Zhao, Seung Yon Rhee
Summary: Pathway enrichment analysis is crucial for interpreting omics datasets and generating hypotheses. This article discusses best practices for interpreting different types of omics data using pathway enrichment analysis and emphasizes the importance of considering intrinsic features of various types of omics data. The article also explains key components that influence the outcomes of pathway enrichment analysis and provides guidance on reporting methodological details to improve reproducibility. It aims to serve as a primer for biologists to utilize omics resources and encourage bioinformatics tool developers to enhance the power of pathway enrichment analysis.
TRENDS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Otto Kauko, Susumu Y. Imanishi, Evgeny Kulesskiy, Laxman Yetukuri, Teemu Daniel Laajala, Mukund Sharma, Karolina Pavic, Anna Aakula, Christian Rupp, Mikael Jumppanen, Pekka Haapaniemi, Luyao Ruan, Bhagwan Yadav, Veronika Suni, Taru Varila, Garry L. Corthals, Juri Reimand, Krister Wennerberg, Tero Aittokallio, Jukka Westermarck
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Esther Rheinbay, Morten Muhlig Nielsen, Federico Abascal, Jeremiah A. Wala, Ofer Shapira, Grace Tiao, Henrik Hornshoj, Julian M. Hess, Randi Istrup Juul, Ziao Lin, Lars Feuerbach, Radhakrishnan Sabarinathan, Tobias Madsen, Jaegil Kim, Loris Mularoni, Shimin Shuai, Andres Lanzos, Carl Herrmann, Yosef E. Maruvka, Ciyue Shen, Samirkumar B. Amin, Pratiti Bandopadhayay, Johanna Bertl, Keith A. Boroevich, John Busanovich, Joana Carlevaro-Fita, Dimple Chakravarty, Calvin Wing Yiu Chan, David Craft, Priyanka Dhingra, Klev Diamanti, Nuno A. Fonseca, Abel Gonzalez-Perez, Qianyun Guo, Mark P. Hamilton, Nicholas J. Haradhvala, Chen Hong, Keren Isaev, Todd A. Johnson, Malene Juul, Andre Kahles, Abdullah Kahraman, Youngwook Kim, Jan Komorowski, Kiran Kumar, Sushant Kumar, Donghoon Lee, Kjong-Van Lehmann, Yilong Li, Eric Minwei Liu, Lucas Lochovsky, Keunchil Park, Oriol Pich, Nicola D. Roberts, Gordon Saksena, Steven E. Schumacher, Nikos Sidiropoulos, Lina Sieverling, Nasa Sinnott-Armstrong, Chip Stewart, David Tamborero, Jose M. C. Tubio, Husen M. Umer, Liis Uuskula-Reimand, Claes Wadelius, Lina Wadi, Xiaotong Yao, Cheng-Zhong Zhang, Jing Zhang, James E. Haber, Asger Hobolth, Marcin Imielinski, Manolis Kellis, Michael S. Lawrence, Christian von Mering, Hidewaki Nakagawa, Benjamin J. Raphael, Mark A. Rubin, Chris Sander, Lincoln D. Stein, Joshua M. Stuart, Tatsuhiko Tsunoda, David A. Wheeler, Rory Johnson, Juri Reimand, Mark Gerstein, Ekta Khurana, Peter J. Campbell, Nuria Lopez-Bigas, Joachim Weischenfeldt, Rameen Beroukhim, Inigo Martincorena, Jakob Skou Pedersen, Gad Getz, Gary D. Bader, Jonathan Barenboim, Soren Brunak, Ken Chen, Jung Kyoon Choi, Jordi Deu-Pons, J. Lynn Fink, Joan Frigola, Carlo Gambacorti-Passerini, Dale W. Garsed, Ivo G. Gut, David Haan, Arif O. Harmanci, Mohamed Helmy, Ermin Hodzic, Jose M. G. Izarzugaza, Jong K. Kim, Jan O. Korbel, Erik Larsson, Shantao Li, Xiaotong Li, Shaoke Lou, Kathleen Marchal, Alexander Martinez-Fundichely, Patrick D. McGillivray, William Meyerson, Ferran Muinos, Marta Paczkowska, Kiejung Park, Tirso Pons, Sergio Pulido-Tamayo, Iker Reyes-Salazar, Matthew A. Reyna, Carlota Rubio-Perez, S. Cenk Sahinalp, Leonidas Salichos, Mark Shackleton, Raunak Shrestha, Alfonso Valencia, Miguel Vazquez, Lieven P. C. Verbeke, Jiayin Wang, Jonathan Warrell, Sebastian M. Waszak, Guanming Wu, Jun Yu, Xuanping Zhang, Yan Zhang, Zhongming Zhao, Lihua Zou, Kadir C. Akdemir, Eva G. Alvarez, Adrian Baez-Ortega, Paul C. Boutros, David D. L. Bowtell, Benedikt Brors, Kathleen H. Burns, Kin Chan, Isidro CortesCiriano, Ana Dueso-Barroso, Andrew J. Dunford, Paul A. Edwards, Xavier Estivill, Dariush Etemadmoghadam, Milana Frenkel-Morgenstern, Dmitry A. Gordenin, Barbara Hutter, David T. W. Jones, Young Seok Ju, Marat D. Kazanov, Leszek J. Klimczak, Youngil Koh, Eunjung Alice Lee, Jake June-Koo Lee, Andy G. Lynch, Geoff Macintyre, Florian Markowetz, Matthew Meyerson, Satoru Miyano, Fabio C. P. Navarro, Stephan Ossowski, Peter J. Park, John Pearson, Montserrat Puiggros, Karsten Rippe, Steven A. Roberts, Bernardo RodriguezMartin, Ralph Scully, David Torrents, Izar Villasante, Nicola Waddell, Lixing Yang, Sung-Soo Yoon, Jorge Zamora
Article
Multidisciplinary Sciences
Matthew A. Reyna, David Haan, Marta Paczkowska, Lieven P. C. Verbeke, Miguel Vazquez, Abdullah Kahraman, Sergio Pulido-Tamayo, Jonathan Barenboim, Lina Wadi, Priyanka Dhingra, Raunak Shrestha, Gad Getz, Michael S. Lawrence, Jakob Skou Pedersen, Mark A. Rubin, David A. Wheeler, Soren Brunak, Jose M. G. Izarzugaza, Ekta Khurana, Kathleen Marchal, Christian von Mering, S. Cenk Sahinalp, Alfonso Valencia, Juri Reimand, Joshua M. Stuart, Benjamin J. Raphael
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Marta Paczkowska, Jonathan Barenboim, Nardnisa Sintupisut, Natalie S. Fox, Helen Zhu, Diala Abd-Rabbo, Miles W. Mee, Paul C. Boutros, Juri Reimand
NATURE COMMUNICATIONS
(2020)
Editorial Material
Biochemistry & Molecular Biology
Eran Segal, Feng Zhang, Xihong Lin, Gary King, Ophir Shalem, Smadar Shilo, William E. Allen, Faisal Alquaddoomi, Han Altae-Tran, Simon Anders, Ran Balicer, Tal Bauman, Ximena Bonilla, Gisel Booman, Andrew T. Chan, Ori Cohen, Silvano Coletti, Natalie Davidson, Yuval Dor, David A. Drew, Olivier Elemento, Georgina Evans, Phil Ewels, Joshua Gale, Amir Gavrieli, Benjamin Geiger, Yonatan H. Grad, Casey S. Greene, Iman Hajirasouliha, Roman Jerala, Andre Kahles, Olli Kallioniemi, Ayya Keshet, Ljupco Kocarev, Gregory Landua, Tomer Meir, Aline Muller, Long H. Nguyen, Matej Oresic, Svetlana Ovchinnikova, Hedi Peterson, Jana Prodanova, Jay Rajagopal, Gunnar Ratsch, Hagai Rossman, Johan Rung, Andrea Sboner, Alexandros Sigaras, Tim Spector, Ron Steinherz, Irene Stevens, Jaak Vilo, Paul Wilmes
Correction
Biochemistry & Molecular Biology
Eran Segal, Feng Zhang, Xihong Lin, Gary King, Ophir Shalem, Smadar Shilo, William E. Allen, Faisal Alquaddoomi, Han Altae-Tran, Simon Anders, Ran Balicer, Tal Bauman, Ximena Bonilla, Gisel Booman, Andrew T. Chan, Ori Cohen, Silvano Coletti, Natalie Davidson, Yuval Dor, David A. Drew, Olivier Elemento, Georgina Evans, Phil Ewels, Joshua Gale, Amir Gavrieli, Benjamin Geiger, Yonatan H. Grad, Casey S. Greene, Iman Hajirasouliha, Roman Jerala, Andre Kahles, Olli Kallioniemi, Ayya Keshet, Ljupco Kocarev, Gregory Landua, Tomer Meir, Aline Muller, Long H. Nguyen, Matej Oresic, Svetlana Ovchinnikova, Hedi Peterson, Jana Prodanova, Jay Rajagopal, Gunnar Raetsch, Hagai Rossman, Johan Rung, Andrea Sboner, Alexandros Sigaras, Tim Spector, Ron Steinherz, Irene Stevens, Jaak Vilo, Paul Wilmes
Article
Biochemical Research Methods
Kim T. Gurwitz, Prakash Singh Gaur, Louisa J. Bellis, Lee Larcombe, Eva Alloza, Balint Laszlo Balint, Alexander Botzki, Jure Dimec, Victoria Dominguez del Angel, Pedro L. Fernandes, Eija Korpelainen, Roland Krause, Mateusz Kuzak, Loredana Le Pera, Brane Leskosek, Jessica M. Lindvall, Diana Marek, Paula A. Martinez, Tuur Muyldermans, Stale Nygard, Patricia M. Palagi, Hedi Peterson, Fotis Psomopoulos, Vojtech Spiwok, Celia W. G. van Gelder, Allegra Via, Marko Vidak, Daniel Wibberg, Sarah L. Morgan, Gabriella Rustici
PLOS COMPUTATIONAL BIOLOGY
(2020)
Article
Biochemical Research Methods
Dmytro Fishman, Ivan Kuzmin, Priit Adler, Jaak Vilo, Hedi Peterson
BMC BIOINFORMATICS
(2020)
Article
Biochemistry & Molecular Biology
Diogo Pellegrina, Alexander T. Bahcheli, Michal Krassowski, Juri Reimand
Summary: This study using machine learning identified genetic variations associated with phosphorylation sites regulated by SARS-CoV-2 infection. These variations were found to be enriched in signaling networks involved in host defenses, reflecting the evolution of host response to SARS-CoV-2 infection. The genetic variations were found in proteins involved in the viral life cycle and host responses, potentially contributing to the comorbidities of COVID-19.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Biochemical Research Methods
Oliver Ocsenas, Juri Reimand
Summary: Somatic mutations in cancer genomes are associated with DNA replication timing and chromatin accessibility. This study uses machine learning to model mutation burden in cancer genomes and finds that the epigenomes of primary cancers are the strongest predictors of mutation burden. The genomic distributions of mutational signatures are also influenced by the epigenomes of matched cancer and tissue types. This study highlights the association of regional mutational processes with the epigenomes of primary cancers.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Liis Kolberg, Uku Raudvere, Ivan Kuzmin, Priit Adler, Jaak Vilo, Hedi Peterson
Summary: g:Profiler is a reliable and up-to-date functional enrichment analysis tool that integrates multiple databases and supports various evidence types, identifier types, and organisms. It provides comprehensive analysis of gene lists and offers interactive user interfaces, custom statistical backgrounds, and programmatic interfaces for easy integration into custom workflows. It supports 849 species and has been available since 2007, with a focus on research reproducibility and transparency. g:Profiler offers valuable resources for genetics, biology, and medical researchers and can be accessed for free at https://biit.cs.ut.ee/gprofiler.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Christian A. Lee, Diala Abd-Rabbo, Juri Reimand
Summary: The study characterized the mutational landscape of 1.3 million gene-regulatory and chromatin architectural elements in 2419 cancer genomes, identifying local mutational processes affecting CTCF binding sites, transcription start sites, and tissue-specific open-chromatin regions. The research also found associations between increased mutation frequency in TSSs with mRNA abundance in most cancer types, and enrichment of mutations in open-chromatin regions. Additionally, specific mutational signature enrichments were detected, such as SBS40 in prostate cancer's open-chromatin regions and SBS17b in CTCF binding sites in gastrointestinal cancers.
Article
Cell Biology
Steffen Moeller, Nadine Saul, Alan A. Cohen, Ruediger Koehling, Sina Sender, Hugo Murua Escobar, Christian Junghanss, Francesca Cirulli, Alessandra Berry, Peter Antal, Priit Adler, Jaak Vilo, Michele Boiani, Ludger Jansen, Dirk Repsilber, Hans Joergen Grabe, Stephan Struckmann, Israel Barrantes, Mohamed Hamed, Brecht Wouters, Liliane Schoofs, Walter Luyten, Georg Fuellen