CF-Seq, an accessible web application for rapid re-analysis of cystic fibrosis pathogen RNA sequencing studies

Neff, Samuel L.; Hampton, Thomas H.; Puerner, Charles; Cengher, Liviu; Doing, Georgia; Lee, Alexandra; Koeppen, Katja; Cheung, Ambrose L.; Hogan, Deborah A.; Cramer, Robert A.

doi:10.1038/s41597-022-01431-1

Cited by 8 publications

(4 citation statements)

References 72 publications

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“…The P. aeruginosa community has long supported the development and widespread use of databases, information hubs, and analysis tools such as the Pseudomonas Genome Database ( 10 ), BACTOME ( 11 ), the International Pseudomonas Consortium Database ( 12 ), the Pseudomonas aeruginosa Metabolome Database ( 13 ), the Pseudomonas aeruginosa transcriptome viewer ( 14 ), and the shiny applications with the algorithmically annotated data sets GAPE ( 15 ) and CF-Seq ( 16 ). Tools have also been developed that utilize public data from many experiments in concert, such as the ADAGE Web server, which enables the exploration of P. aeruginosa gene expression microarray data after processing by a machine learning algorithm ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Computationally Efficient Assembly of Pseudomonas aeruginosa Gene Expression Compendia

et al. 2023

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Section: Introductionmentioning

confidence: 99%

Computationally Efficient Assembly of Pseudomonas aeruginosa Gene Expression Compendia

et al. 2023

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“…The Rocket-miR application adds to our suite of existing community-oriented bioinformatics toolsincluding three other R shiny applications (ScanGEO, GAPE, CF-Seq) that make insights from public transcriptomic data on human pathogens more accessible to non-computational scientists, and a fourth (ESKAPE Act Plus) that enables researchers without bioinformatics experience to perform pathway activation analysis for ESKAPE pathogens (105)(106)(107)(108). We envision Rocket-miR and these other applications as ongoing projectstools that researchers studying any microbial pathogen can use and extend, to the ultimate benefit of patients with drug-resistant infections.…”

Section: Discussionmentioning

confidence: 99%

Rocket-miR, a Translational Launchpad for miRNA-based Antimicrobial Drug Development

Neff¹,

Hampton²,

Koeppen³

et al. 2023

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Developing software tools that leverage biological datasets to accelerate drug discovery is an important aspect of bioinformatics research. Here we present a novel example: a web application called Rocket-miR that applies an existing bioinformatics algorithm (IntaRNA) to predict cross-species miRNA-mRNA interactions and identify human miRNAs with potential antimicrobial activity against antibiotic resistant bacterial infections. Rocket-miR is the logical extension of our prior finding that human miRNA let-7b-5p impairs the ability of the ubiquitous opportunistic pathogen P. aeruginosa to form biofilms and resist the bactericidal effect of beta lactam antibiotics. Rocket-miR's point and click interface enables researchers without programming expertise to predict additional human-miRNA-pathogen interactions. Identified miRNAs can be developed into novel antimicrobials effective against the 24 clinically relevant pathogens, implicated in diseases of the lung, gut and other organs, that are included in the application. The manuscript incorporates three case studies contributed by microbiologists that study human pathogens to demonstrate the usefulness and usability of the application. Rocket-miR is accessible at the following link: http://scangeo.dartmouth.edu/RocketmiR/.

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“…Similar models should be developed for other pathogens, of the lung, gut, and other organs, for CF and other diseases. Furthermore, the construction of compendia that identify and characterize all gene expression datasets for pathogens relevant to CF (and other diseases) are also useful in laying the grounds for future model development (69)(70)(71).…”

Section: Discussionmentioning

confidence: 99%

Analysis ofPseudomonas aeruginosatranscription in anex vivocystic fibrosis sputum model identifies metal restriction as a gene expression stimulus

Neff,

Doing,

Reiter

et al. 2023

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ChronicPseudomonas aeruginosalung infections are a distinctive feature of cystic fibrosis (CF) pathology, that challenge adults with CF even with the advent of highly effective modulator therapies. CharacterizingP. aeruginosatranscription in the CF lung and identifying factors that drive gene expression could yield novel strategies to eradicate infection or otherwise improve outcomes. To complement publishedP. aeruginosagene expression studies in laboratory culture models designed to model the CF lung environment, we employed an ex vivo sputum model in which laboratory strain PAO1 was incubated in sputum from different CF donors. As part of the analysis, we compared PAO1 gene expression in this “spike-in” sputum model to that forP. aeruginosagrown in artificial sputum medium (ASM). Analyses focused on genes that were differentially expressed between sputum and ASM and genes that were most highly expressed in sputum. We present a new approach that used sets of genes with correlated expression, identified by the gene expression analysis tool eADAGE, to analyze the differential activity of pathways inP. aeruginosagrown in CF sputum from different individuals. A key characteristic ofP. aeruginosagrown in expectorated CF sputum was related to zinc and iron acquisition, but this signal varied by donor sputum. In addition, a significant correlation betweenP. aeruginosaexpression of the H1-type VI secretion system and corrector use by the sputum donor was observed. These methods may be broadly useful in looking for variable signals across clinical samples.ImportanceIdentifying the gene expression programs used byPseudomonas aeruginosato colonize the lungs of people with cystic fibrosis (CF) will illuminate new therapeutic strategies. To capture these transcriptional programs, we cultured the commonP. aeruginosalaboratory strain PAO1 in expectorated sputum from CF patient donors. Through bioinformatics analysis, we defined sets of genes that are more transcriptionally active in real CF sputum compared to artificial sputum media (ASM). Many of the most differentially active gene sets contained genes related to metal acquisition, suggesting that these gene sets play an active role in scavenging for metals in the CF lung environment which is inadequately represented in ASM. Future studies ofP. aeruginosatranscription in CF may benefit from the use of an expectorated sputum model or modified forms of ASM supplemented with metals.

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CF-Seq, an accessible web application for rapid re-analysis of cystic fibrosis pathogen RNA sequencing studies

Cited by 8 publications

References 72 publications

Computationally Efficient Assembly of Pseudomonas aeruginosa Gene Expression Compendia

Computationally Efficient Assembly of Pseudomonas aeruginosa Gene Expression Compendia

Rocket-miR, a Translational Launchpad for miRNA-based Antimicrobial Drug Development

Analysis ofPseudomonas aeruginosatranscription in anex vivocystic fibrosis sputum model identifies metal restriction as a gene expression stimulus

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