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1. PTMViz: a tool for analyzing and visualizing histone post translational modification data

   https://doi.org/10.1186/s12859-021-04166-9  

   Chappell, Kevin ; Graw, Stefan ; Washam, Charity L. ; Storey, Aaron J. ; Bolden, Chris ; Peterson, Eric C. ; Byrum, Stephanie D. ( May 2021 , BMC Bioinformatics)

   Histone post-translational modifications (PTMs) play an important role in our system by regulating the structure of chromatin and therefore contribute to the regulation of gene and protein expression. Irregularities in histone PTMs can lead to a variety of different diseases including various forms of cancer. Histone modifications are analyzed using high resolution mass spectrometry, which generate large amounts of data that requires sophisticated bioinformatics tools for analysis and visualization. PTMViz is designed for downstream differential abundance analysis and visualization of both protein and/or histone modifications.

   PTMViz provides users with data tables and visualization plots of significantly differentiated proteins and histone PTMs between two sample groups. All the data is packaged into interactive data tables and graphs using the Shiny platform to help the user explore the results in a fast and efficient manner to assess if changes in the system are due to protein abundance changes or epigenetic changes. In the example data provided, we identified several proteins differentially regulated in the dopaminergic pathway between mice treated with methamphetamine compared to a saline control. We also identified histone post-translational modifications including histone H3K9me, H3K27me3, H4K16ac, and that were regulated due to drug exposure.

   Histone modifications play an integral rolemore »in the regulation of gene expression. PTMViz provides an interactive platform for analyzing proteins and histone post-translational modifications from mass spectrometry data in order to quickly identify differentially expressed proteins and PTMs.

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2. The Epidermal Microbiome Within an Aggregation of Leopard Sharks (Triakis semifasciata) Has Taxonomic Flexibility with Gene Functional Stability Across Three Time-points

   https://doi.org/10.1007/s00248-022-01969-y  

   Doane, Michael P. ; Johnson, Colton J. ; Johri, Shaili ; Kerr, Emma N. ; Morris, Megan M. ; Desantiago, Ric ; Turnlund, Abigail C. ; Goodman, Asha ; Mora, Maria ; Lima, Laís Farias Oliveira ; et al ( February 2022 , Microbial Ecology)

   The epidermis of Chondrichthyan fishes consists of dermal denticles with production of minimal but protein-rich mucus that collectively, influence the attachment and biofilm development of microbes, facilitating a unique epidermal microbiome. Here, we use metagenomics to provide the taxonomic and functional characterization of the epidermal microbiome of theTriakis semifasciata(leopard shark) at three time-points collected across 4 years to identify links between microbial groups and host metabolism. Our aims include (1) describing the variation of microbiome taxa over time and identifying recurrent microbiome members (present across all time-points); (2) investigating the relationship between the recurrent and flexible taxa (those which are not found consistently across time-points); (3) describing the functional compositions of the microbiome which may suggest links with the host metabolism; and (4) identifying whether metabolic processes are shared across microbial genera or are unique to specific taxa. Microbial members of the microbiome showed high similarity between all individuals (Bray–Curtis similarity index = 82.7, where 0 = no overlap, 100 = total overlap) with the relative abundance of those members varying across sampling time-points, suggesting flexibility of taxa in the microbiome. One hundred and eighty-eight genera were identified as recurrent, includingPseudomonas,Erythrobacter,Alcanivorax,Marinobacter, andSphingopxisbeing consistently abundant across time-points, whileLimnobacterandXyellaexhibited switching patterns with high relative abundance in 2013,SphingobiumandSphingomonain 2015,more »andAltermonas,Leeuwenhoekiella,Gramella, andMaribacterin 2017. Of the 188 genera identified as recurrent, the top 19 relatively abundant genera formed three recurrent groups. The microbiome also displayed high functional similarity between individuals (Bray–Curtis similarity index = 97.6) with gene function composition remaining consistent across all time-points. These results show that while the presence of microbial genera exhibits consistency across time-points, their abundances do fluctuate. Microbial functions however remain stable across time-points; thus, we suggest the leopard shark microbiomes exhibit functional redundancy. We show coexistence of microbes hosted in elasmobranch microbiomes that encode genes involved in utilizing nitrogen, but not fixing nitrogen, degrading urea, and resistant to heavy metal.

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3. iDINGO—integrative differential network analysis in genomics with Shiny application

   https://doi.org/10.1093/bioinformatics/btx750  

   Class, Caleb A. ; Ha, Min Jin ; Baladandayuthapani, Veerabhadran ; Do, Kim-Anh ; Berger, ed., Bonnie ( November 2017 , Bioinformatics)

   Differential network analysis is an important way to understand network rewiring involved in disease progression and development. Building differential networks from multiple ‘omics data provides insight into the holistic differences of the interactive system under different patient-specific groups. DINGO was developed to infer group-specific dependencies and build differential networks. However, DINGO and other existing tools are limited to analyze data arising from a single platform, and modeling each of the multiple ‘omics data independently does not account for the hierarchical structure of the data.

   We developed the iDINGO R package to estimate group-specific dependencies and make inferences on the integrative differential networks, considering the biological hierarchy among the platforms. A Shiny application has also been developed to facilitate easier analysis and visualization of results, including integrative differential networks and hub gene identification across platforms.

   R package is available on CRAN (https://cran.r-project.org/web/packages/iDINGO) and Shiny application at https://github.com/MinJinHa/iDINGO.

   Supplementary data are available at Bioinformatics online.
4. Inhibitory Bacterial Diversity and Mucosome Function Differentiate Susceptibility of Appalachian Salamanders to Chytrid Fungal Infection

   https://doi.org/10.1128/aem.01818-21  

   Jiménez, Randall R. ; Carfagno, Amy ; Linhoff, Luke ; Gratwicke, Brian ; Woodhams, Douglas C. ; Chafran, Liana Soares ; Bletz, Molly C. ; Bishop, Barney ; Muletz-Wolz, Carly R. ( April 2022 , Applied and Environmental Microbiology)

   Reguera, Gemma (Ed.)

   ABSTRACT Mucosal defenses are crucial in animals for protection against pathogens and predators. Host defense peptides (antimicrobial peptides, AMPs) as well as skin-associated microbes are key components of mucosal immunity, particularly in amphibians. We integrate microbiology, molecular biology, network-thinking, and proteomics to understand how host and microbially derived products on amphibian skin (referred to as the mucosome) serve as pathogen defenses. We studied defense mechanisms against chytrid pathogens, Batrachochytrium dendrobatidis (Bd) and B. salamandrivorans (Bsal), in four salamander species with different Batrachochytrium susceptibilities. Bd infection was quantified using qPCR, mucosome function (i.e., ability to kill Bd or Bsal zoospores in vitro ), skin bacterial communities using 16S rRNA gene amplicon sequencing, and the role of Bd-inhibitory bacteria in microbial networks across all species. We explored the presence of candidate-AMPs in eastern newts and red-backed salamanders. Eastern newts had the highest Bd prevalence and mucosome function, while red-back salamanders had the lowest Bd prevalence and mucosome function, and two-lined salamanders and seal salamanders were intermediates. Salamanders with highest Bd infection intensity showed greater mucosome function. Bd infection prevalence significantly decreased as putative Bd-inhibitory bacterial richness and relative abundance increased on hosts. In co-occurrence networks, some putative Bd-inhibitory bacteria were found asmore »hub-taxa, with red-backs having the highest proportion of protective hubs and positive associations related to putative Bd-inhibitory hub bacteria. We found more AMP candidates on salamanders with lower Bd susceptibility. These findings suggest that salamanders possess distinct innate mechanisms that affect chytrid fungi. IMPORTANCE How host mucosal defenses interact, and influence disease outcome is critical in understanding host defenses against pathogens. A more detailed understanding is needed of the interactions between the host and the functioning of its mucosal defenses in pathogen defense. This study investigates the variability of chytrid susceptibility in salamanders and the innate defenses each species possesses to mediate pathogens, thus advancing the knowledge toward a deeper understanding of the microbial ecology of skin-associated bacteria and contributing to the development of bioaugmentation strategies to mediate pathogen infection and disease. This study improves the understanding of complex immune defense mechanisms in salamanders and highlights the potential role of the mucosome to reduce the probability of Bd disease development and that putative protective bacteria may reduce likelihood of Bd infecting skin.« less
5. Predicting gene structure changes resulting from genetic variants via exon definition features

   https://doi.org/10.1093/bioinformatics/bty324  

   Majoros, William H. ; Holt, Carson ; Campbell, Michael S. ; Ware, Doreen ; Yandell, Mark ; Reddy, Timothy E. ; Birol, ed., Inanc ( April 2018 , Bioinformatics)

   Genetic variation that disrupts gene function by altering gene splicing between individuals can substantially influence traits and disease. In those cases, accurately predicting the effects of genetic variation on splicing can be highly valuable for investigating the mechanisms underlying those traits and diseases. While methods have been developed to generate high quality computational predictions of gene structures in reference genomes, the same methods perform poorly when used to predict the potentially deleterious effects of genetic changes that alter gene splicing between individuals. Underlying that discrepancy in predictive ability are the common assumptions by reference gene finding algorithms that genes are conserved, well-formed and produce functional proteins.

   We describe a probabilistic approach for predicting recent changes to gene structure that may or may not conserve function. The model is applicable to both coding and non-coding genes, and can be trained on existing gene annotations without requiring curated examples of aberrant splicing. We apply this model to the problem of predicting altered splicing patterns in the genomes of individual humans, and we demonstrate that performing gene-structure prediction without relying on conserved coding features is feasible. The model predicts an unexpected abundance of variants that create de novo splice sites, an observationmore »supported by both simulations and empirical data from RNA-seq experiments. While these de novo splice variants are commonly misinterpreted by other tools as coding or non-coding variants of little or no effect, we find that in some cases they can have large effects on splicing activity and protein products and we propose that they may commonly act as cryptic factors in disease.

   The software is available from geneprediction.org/SGRF.

   Supplementary information is available at Bioinformatics online.

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