Article
Biochemical Research Methods
Nikolas Dovrolis, Katerina Kassela, Konstantinos Konstantinidis, Adamantia Kouvela, Stavroula Veletza, Ioannis Karakasiliotis
Summary: The study of viruses' genetic composition is crucial for their identification and classification, especially during times of pandemic turmoil. New technologies in nucleic acid sequencing can introduce artifacts into viral genomes, and this study proposes an algorithm to help remove problematic regions while retaining essential genetic information. This approach aims to improve the accuracy and integrity of viral genomes for novel virus identification and characterization in public databases.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Julianne K. David, Sean K. Maden, Mary A. Wood, Reid F. Thompson, Abhinav Nellore
Summary: Short-read tools for detecting intron retention have poor performance and often result in false positives and false negatives, calling into question the completeness and validity of putatively retained introns called by commonly used methods.
Article
Biotechnology & Applied Microbiology
Yu Hu, Li Fang, Xuelian Chen, Jiang F. Zhong, Mingyao Li, Kai Wang
Summary: LIQA is a tool for long-read RNA sequencing data that quantifies isoform expression and detects differential alternative splicing events, demonstrating high accuracy in various experimental datasets.
Article
Biochemical Research Methods
Malte D. Luecken, M. Buettner, K. Chaichoompu, A. Danese, M. Interlandi, M. F. Mueller, D. C. Strobl, L. Zappia, M. Dugas, M. Colome-Tatche, Fabian J. Theis
Summary: This study benchmarked 68 method and preprocessing combinations on 85 batches of gene expression data, highlighting the importance of highly variable gene selection in improving method performance. When dealing with complex integration tasks, scANVI, Scanorama, scVI, and scGen consistently performed well, while the performance of single-cell ATAC-sequencing integration was strongly influenced by the choice of feature space.
Article
Biochemical Research Methods
Huiguang Yi, Yanling Lin, Qing Chang, Wenfei Jin
Summary: Alignment-based RNA-seq quantification methods involve time-consuming alignment process, while alignment-free RNA-seq quantification methods bypass this step and achieve significant speed improvements. However, existing alignment-free methods relying on EM algorithm only provide locally optimal solutions, leaving room for further accuracy improvement. In this study, we introduce TQSLE, the first alignment-free RNA-seq quantification method providing a globally optimal solution for transcript abundances estimation. TQSLE outperforms other alignment-free methods in terms of accuracy, while maintaining comparable speed. TQSLE is freely available.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemical Research Methods
Lu Pan, Huy Q. Dinh, Yudi Pawitan, Trung Nghia Vu
Summary: In this study, we developed an isoform-level quantification method for high-throughput single-cell RNA sequencing by utilizing transcription clusters and isoform paralogs. The method, called Scasa, performed well in simulations and revealed a subgroup of monocytes missed by gene-based methods in a reanalysis of a CITE-Seq dataset.
Article
Biochemistry & Molecular Biology
Kez Cleal, Duncan M. Baird
Summary: Structural variation (SV) is important in genome evolution and disease, and Dysgu is a tool that accurately detects SVs using paired-end or long-read sequencing, with high sensitivity and fast running speed.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemical Research Methods
Hongyang Li, Ridvan Eksi, Daiyao Yi, Bradley Godfrey, Lisa R. Mathew, Christopher L. O'Connor, Markus Bitzer, Matthias Kretzler, Rajasree Menon, Yuanfang Guan
Summary: Studying isoform expression at the microscopic level is a challenging task. In this study, a pipeline combining experimental and computational methods was developed to identify isoforms in the glomerular and tubulo-interstitial compartments of the kidney. Distinct functional pathways were found in these two compartments, providing important resources for kidney research.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pedro L. Baldoni, Yunshun Chen, Soroor Hediyeh-zadeh, Yang Liao, Xueyi Dong, Matthew E. Ritchie, Wei Shi, Gordon K. Smyth
Summary: Differential expression analysis of RNA-seq is commonly used in bioinformatics. However, transcript-level quantifications are more uncertain due to the ambiguity of sequence reads. To address this issue, a new method is proposed to estimate the overdispersion caused by read-to-transcript ambiguity and generate scaled transcript counts, which improves the efficiency and accuracy of differential analysis.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Christian Vogeley, Thach Nguyen, Selina Woeste, Jean Krutmann, Thomas Haarmann-Stemmann, Andrea Rossi
Summary: Transcriptome analysis experiments provide valuable insights into cell physiology and disease mechanisms. Oxford Nanopore Technologies (ONT) offers a fast, portable, and cost-effective alternative to next-generation sequencing (NGS). However, the availability of RNA-Seq data analysis software that is user-friendly and allows ONT data analysis without bioinformatics expertise is limited. To address this, we developed Duesselpore (TM), a user-friendly deep sequencing workflow that runs as a local webserver and enables ONT and NGS data analysis without the need for additional tools or internet connection.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
A. Sina Booeshaghi, Zizhen Yao, Cindy van Velthoven, Kimberly Smith, Bosiljka Tasic, Hongkui Zeng, Lior Pachter
Summary: Full-length SMART-seq(l) single-cell RNA sequencing can identify isoform markers for different cell types and enable spatially resolved isoform expression inference. Multi-platform analysis reveals isoform specificity in cell types and improves the comprehensive atlas of transcription in the mouse primary motor cortex.
Article
Multidisciplinary Sciences
Hai C. T. Nguyen, Bukyung Baik, Sora Yoon, Taesung Park, Dougu Nam
Summary: This study evaluates the integration of single-cell RNA sequencing data and suggests high-performance methods under different conditions. Batch effects, sequencing depth, and data sparsity significantly impact the analysis performance. The use of batch-corrected data rarely improves the analysis for sparse data, while batch covariate modeling improves the analysis for substantial batch effects. Several high-performance methods are proposed based on simulation and real data analyses.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Karolis Ramanauskas, Boris Igic
Summary: kakapo is a Python-based pipeline that allows users to extract and assemble specified genes or gene families. It can flexibly process original RNA-seq reads or GenBank SRA accession inputs without the need for global assembly. The pipeline identifies open reading frames in the gene transcripts and annotates them, and it can also filter out reads from non-target organisms.
Correction
Biotechnology & Applied Microbiology
Jong Ghut Ashley Aw, Shaun W. Lim, Jia Xu Wang, Finnlay R. P. Lambert, Wen Ting Tan, Yang Shen, Yu Zhang, Pornchai Kaewsapsak, Chenhao Li, Sarah B. Ng, Leah A. Vardy, Meng How Tan, Niranjan Nagarajan, Yue Wan
Summary: A correction to this paper has been published and readers can find the updated content at the following link: https://doi.org/10.1038/s41587-021-00889-5.
NATURE BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Qingwang Chen, Yaqing Liu, Yuechen Gao, Ruolan Zhang, Wanwan Hou, Zehui Cao, Yi-Zhou Jiang, Yuanting Zheng, Leming Shi, Ding Ma, Jingcheng Yang, Zhi-Ming Shao, Ying Yu
Summary: The study presents a molecular subtyping method for triple-negative breast cancer and provides a multiomics dataset consisting of clinical, genomic, and transcriptomic information. This work contributes to a better understanding of the mechanisms of this breast cancer type, identification of actionable targets, and offers a user-friendly database for data access and exploration.
Article
Biology
Shaon Sengupta, Thomas G. Brooks, Gregory R. Grant, Garret A. FitzGerald
Summary: The COVID-19 pandemic has sparked collaborative efforts and novel approaches across disciplines, with circadian biology potentially playing a role in guiding diagnostic and therapeutic strategies as our understanding of its integration into clinical practice continues to evolve.
JOURNAL OF BIOLOGICAL RHYTHMS
(2021)
Article
Biology
Yasmine Issah, Amruta Naik, Soon Y. Tang, Kaitlyn Forrest, Thomas G. Brooks, Nicholas Lahens, Katherine N. Theken, Mara Mermigos, Amita Sehgal, George S. Worthen, Garret A. FitzGerald, Shaon Sengupta
Summary: Early-life exposure to neonatal hyperoxia eliminates the clock-mediated protection against influenza A virus infection in mice, mainly through dysregulation of the lung intrinsic clock. Loss of the circadian protein Bmal1 in AT2 cells recapitulates the increased mortality and loss of temporal gating observed in animals exposed to hyperoxia. These findings suggest a novel role for the circadian clock in AT2 cells in mediating the long-term effects of early-life exposures to the lungs.
Article
Multidisciplinary Sciences
Barry Slaff, Caleb M. Radens, Paul Jewell, Anupama Jha, Nicholas F. Lahens, Gregory R. Grant, Andrei Thomas-Tikhonenko, Kristen W. Lynch, Yoseph Barash
Summary: Confounding factors on gene expression analysis have been extensively studied, while there is a lack of equivalent analysis and tools for RNA splicing; the authors develop an algorithm called MOCCASIN to correct the effect of known and unknown confounders on RNA splicing quantification.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Nicholas F. Lahens, Thomas G. Brooks, Dimitra Sarantopoulou, Soumyashant Nayak, Cris Lawrence, Antonijo Mrcela, Anand Srinivasan, Jonathan Schug, John B. Hogenesch, Yoseph Barash, Gregory R. Grant
Summary: CAMPAREE, a simulator developed in Python, provides flexibility for users by separating input sample modeling from library preparation/sequencing, allowing for incorporation of new biological findings and developments in sequencing technologies. By simulating at the level of individual molecules, CAMPAREE has the potential to model a heterogeneous population of transcripts from the same genes with different states of degradation and processing.
Article
Biology
Thomas G. Brooks, Antonijo Mrcela, Nicholas F. Lahens, Georgios K. Paschos, Tilo Grosser, Carsten Skarke, Garret A. FitzGerald, Gregory R. Grant
Summary: Circadian omics analysis presents a large amount of data and analysis options, with visualization being crucial. Nitecap offers an intuitive and unified web-based solution for this issue.
JOURNAL OF BIOLOGICAL RHYTHMS
(2022)
Article
Psychiatry
Eline T. Luning Prak, Thomas Brooks, Walid Makhoul, Joanne C. Beer, Ling Zhao, Tommaso Girelli, Carsten Skarke, Yvette Sheline
Summary: Late-life depression is associated with inflammation, but the immune dysregulation caused by comorbid medical conditions may play a role. The study found that depression itself does not lead to elevated cytokine levels, and celecoxib may not be effective as an adjunctive antidepressant in older patients without medical reasons for inflammation.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Cell Biology
Sean T. Anderson, Hu Meng, Thomas G. Brooks, Soon Yew Tang, Ronan Lordan, Arjun Sengupta, Soumyashant Nayak, Antonijo Mrela, Dimitra Sarantopoulou, Nicholas F. Lahens, Aalim Weljie, Gregory R. Grant, Frederic D. Bushman, Garret A. FitzGerald
Summary: Longitudinal studies suggest a relationship between shiftwork and cardiometabolic disorders, but the causes and mechanisms are not clear. We developed a mouse model to study circadian misalignment in both sexes and found that female mice showed preserved rhythmicity and were protected from the cardiometabolic effects of misalignment on a high-fat diet. Differences were observed in the liver transcriptome and proteome, as well as gut microbiome dysbiosis, which only occurred in male mice. Antibiotic treatment reduced the impact of misalignment. In the UK Biobank, female shiftworkers demonstrated stronger circadian rhythmicity and a lower incidence of metabolic syndrome compared to males. Our findings suggest that females are more resilient to chronic circadian misalignment, and this difference is conserved in humans.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biology
Thomas G. Brooks, Aditi Manjrekar, Antonijo Mrcela, Gregory R. Grant
Summary: In order to evaluate the consistency of biological rhythms across different studies, 57 public mouse liver tissue time series were analyzed, containing a total of 1096 RNA-seq samples. Only the control groups of each study were included to ensure comparability. Technical factors in RNA-seq library preparation were found to have the greatest influence on transcriptome-level differences. Core clock genes exhibited remarkable consistency in phase across all studies. The overlap of rhythmic genes identified in different studies was generally low.
JOURNAL OF BIOLOGICAL RHYTHMS
(2023)
Article
Multidisciplinary Sciences
Thomas G. Brooks, Nicholas F. Lahens, Gregory R. Grant, Yvette I. Sheline, Garret A. Fitzgerald, Carsten Skarke
Summary: Many chronic diseases are characterized by disrupted sleep-wake cycles, indicating disrupted biorhythms. In this study, the association between wrist temperature amplitudes and future disease onset was investigated. It was found that decreased wrist temperature amplitudes were significantly associated with various diseases, suggesting peripheral thermoregulation as a potential digital biomarker.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Amruta Naik, Kaitlyn M. Forrest, Oindrila Paul, Yasmine Issah, Utham K. Valekunja, Soon Y. Tang, Akhilesh B. Reddy, Elizabeth J. Hennessy, Thomas G. Brooks, Fatima Chaudhry, Apoorva Babu, Michael Morley, Jarod A. Zepp, Gregory R. Grant, Garret A. Fitzgerald, Amita Sehgal, G. Scott Worthen, David B. Frank, Edward E. Morrisey, Shaon Sengupta
Summary: This study demonstrates an association between circadian rhythms and morbidity from lower respiratory tract infections, including hospitalization and mortality even after adjusting for confounding factors. The disruption of the circadian clock impairs lung organoid’s regenerative capacity, and the circadian clock mediates lung regeneration through distinct pathways. The findings suggest that incorporating circadian rhythms into lung repair and regeneration could lead to novel therapies.
Article
Medicine, Research & Experimental
Soon Y. Tang, Hu Meng, Sean T. Anderson, Dimitra Sarantopoulou, Soumita Ghosh, Nicholas F. Lahens, Katherine N. Theken, Emanuela Ricciotti, Elizabeth J. Hennessy, Vincent Tu, Kyle Bittinger, Aalim M. Weiljie, Gregory R. Grant, Garret A. FitzGerald
Summary: Inhibitors of microsomal prostaglandin E synthase 1 (mPGES-1) show potential in clinical development, but may lead to increased blood pressure response to salt loading in male mice, with the compensatory role of atrial natriuretic peptide (ANP) restrained hypertension. Conversely, female mice do not exhibit this hypertensive response, with estrogen compensating for the deficiency in prostacyclin (PGI2). This suggests a potential risk of hypertensive response to mPGES-1 inhibitors in men with hyperlipidemia on a high-salt diet.
JOURNAL OF CLINICAL INVESTIGATION
(2021)