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1. MRHCA: a nonparametric statistics based method for hub and co‐expression module identification in large gene co‐expression network

   https://doi.org/10.1007/s40484-018-0131-z  

   Zhang, Yu ; Cao, Sha ; Zhao, Jing ; Alsaihati, Burair ; Ma, Qin ; Zhang, Chi ( March 2018 , Quantitative Biology)

   Gene co‐expression and differential co‐expression analysis has been increasingly used to study co‐functional and co‐regulatory biological mechanisms from large scale transcriptomics data sets.

   In this study, we develop a nonparametric approach to identify hub genes and modules in a large co‐expression network with low computational and memory cost, namely MRHCA.

   We have applied the method to simulated transcriptomics data sets and demonstrated MRHCA can accurately identify hub genes and estimate size of co‐expression modules. With applying MRHCA and differential co‐expression analysis toE. coliand TCGA cancer data, we have identified significant condition specific activated genes inE. coliand distinct gene expression regulatory mechanisms between the cancer types with high copy number variation and small somatic mutations.

   Our analysis has demonstrated MRHCA can (i) deal with large association networks, (ii) rigorously assess statistical significance for hubs and module sizes, (iii) identify co‐expression modules with low associations, (iv) detect small and significant modules, and (v) allow genes to be present in more than one modules, compared with existing methods.

    

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2. Transcriptomic analyses during development reveal mechanisms of integument structuring and color production

   https://doi.org/10.1007/s10682-023-10256-2  

   Stuckert, Adam M. ; Freeborn, Layla ; Howell, Kimberly A. ; Yang, Yusan ; Nielsen, Rasmus ; Richards-Zawacki, Corinne ; MacManes, Matthew D. ( September 2023 , Evolutionary Ecology)

   Skin coloration and patterning play a key role in animal survival and reproduction. As a result, color phenotypes have generated intense research interest. In aposematic species, color phenotypes can be important in avoiding predation and in mate choice. However, we still know little about the underlying genetic mechanisms of color production, particularly outside of a few model organisms. Here we seek to understand the genetic mechanisms underlying the production of different colors and how these undergo shifting expression patterns throughout development. To answer this, we examine gene expression of two different color patches(yellow and green) in a developmental time series from young tadpoles through adults in the poison frogOophaga pumilio.We identified six genes that were differentially expressed between color patches in every developmental stage (casq1, hand2, myh8, prva, tbx3,andzic1).Of these,hand2, myh8, tbx3,andzic1have either been identified or implicated as important in coloration in other taxa.Casq1andprvabuffer Ca²⁺and are a Ca²⁺transporter, respectively, and may play a role in preventing autotoxicity to pumiliotoxins, which inhibit Ca²⁺-ATPase activity. We identify further candidate genes (e.g.,adh, aldh1a2, asip, lef1, mc1r, tyr, tyrp1, xdh), and identify a suite of hub genes that likely play a key role in integumental reorganization during development (e.g., collagen type I–IV genes, lysyl oxidases) which may also affect coloration via structural organization of chromatophores that contribute to color and pattern. Overall, we identify the putative role of a suite of candidate genes in the production of different color types in a polytypic, aposematic species.

    

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3. Sex-biased and parental allele-specific gene regulation by KDM6A

   https://doi.org/10.1186/s13293-022-00452-0  

   Ma, Wenxiu ; Fang, He ; Pease, Nicolas ; Filippova, Galina N. ; Disteche, Christine M. ; Berletch, Joel B. ( December 2022 , Biology of Sex Differences)

   Abstract Background KDM6A is a demethylase encoded by a gene with female-biased expression due to escape from X inactivation. Its main role is to facilitate gene expression through removal of the repressive H3K27me3 mark, with evidence of some additional histone demethylase-independent functions. KDM6A mutations have been implicated in congenital disorders such as Kabuki Syndrome, as well as in sex differences in cancer. Methods Kdm6a was knocked out using CRISPR/Cas9 gene editing in F1 male and female mouse embryonic stem cells (ES) derived from reciprocal crosses between C57BL6 x Mus castaneus . Diploid and allelic RNA-seq analyses were done to compare gene expression between wild-type and Kdm6a knockout (KO) clones. The effects of Kdm6a KO on sex-biased gene expression were investigated by comparing gene expression between male and female ES cells. Changes in H3K27me3 enrichment and chromatin accessibility at promoter regions of genes with expression changes were characterized by ChIP-seq and ATAC-seq followed by diploid and allelic analyses. Results We report that Kdm6a KO in male and female embryonic stem (ES) cells derived from F1 hybrid mice cause extensive gene dysregulation, disruption of sex biases, and specific parental allele effects. Among the dysregulated genes are candidate genes that may explain abnormal developmental features of Kabuki syndrome caused by KDM6A mutations in human. Strikingly, Kdm6a knockouts result in a decrease in sex-biased expression and in preferential downregulation of the maternal alleles of a number of genes. Most promoters of dysregulated genes show concordant epigenetic changes including gain of H3K27me3 and loss of chromatin accessibility, but there was less concordance when considering allelic changes. Conclusions Our study reveals new sex-related roles of KDM6A in the regulation of developmental genes, the maintenance of sex-biased gene expression, and the differential expression of parental alleles. 

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4. Deep Transcriptomic Analysis Reveals the Dynamic Developmental Progression during Early Development of Channel Catfish (Ictalurus punctatus)

   https://doi.org/10.3390/ijms21155535  

   Ma, Xiaoli ; Su, Baofeng ; Tian, Yuan ; Backenstose, Nathan ; Ye, Zhi ; Moss, Anthony ; Duong, Thuy-Yen ; Wang, Xu ; Dunham, Rex ( August 2020 , International Journal of Molecular Sciences)

   The transition from fertilized egg to larva in fish is accompanied with various biological processes. We selected seven early developmental stages in channel catfish, Ictalurus punctatus, for transcriptome analysis, and covered 22,635 genes with 590 million high-quality RNA-sequencing (seq) reads. Differential expression analysis between neighboring developmental timepoints revealed significantly enriched biological categories associated with growth, development and morphogenesis, which was most evident at 2 vs. 5 days post fertilization (dpf) and 5 vs. 6 dpf. A gene co-expression network was constructed using the Weighted Gene Co-expression Network Analysis (WGCNA) approach and four critical modules were identified. Among candidate hub genes, GDF10, FOXA2, HCEA and SYCE3 were involved in head formation, egg development and the transverse central element of synaptonemal complexes. CK1, OAZ2, DARS1 and UBE2V2 were mainly associated with regulation of cell cycle, growth, brain development, differentiation and proliferation of enterocytes. IFI44L and ZIP10 were critical for the regulation of immune activity and ion transport. Additionally, TCK1 and TGFB1 were related to phosphate transport and regulating cell proliferation. All these genes play vital roles in embryogenesis and regulation of early development. These results serve as a rich dataset for functional genomic studies. Our work reveals new insights of the underlying mechanisms in channel catfish early development. 

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5. Multi-omic characterization of the thermal stress phenome in the stony coral Montipora capitata

   https://doi.org/10.7717/peerj.12335  

   Williams, Amanda ; Pathmanathan, Jananan S. ; Stephens, Timothy G. ; Su, Xiaoyang ; Chiles, Eric N. ; Conetta, Dennis ; Putnam, Hollie M. ; Bhattacharya, Debashish ( January 2021 , PeerJ)

   Background Corals, which form the foundation of biodiverse reef ecosystems, are under threat from warming oceans. Reefs provide essential ecological services, including food, income from tourism, nutrient cycling, waste removal, and the absorption of wave energy to mitigate erosion. Here, we studied the coral thermal stress response using network methods to analyze transcriptomic and polar metabolomic data generated from the Hawaiian rice coral Montipora capitata . Coral nubbins were exposed to ambient or thermal stress conditions over a 5-week period, coinciding with a mass spawning event of this species. The major goal of our study was to expand the inventory of thermal stress-related genes and metabolites present in M. capitata and to study gene-metabolite interactions. These interactions provide the foundation for functional or genetic analysis of key coral genes as well as provide potentially diagnostic markers of pre-bleaching stress. A secondary goal of our study was to analyze the accumulation of sex hormones prior to and during mass spawning to understand how thermal stress may impact reproductive success in M. capitata . Methods M. capitata was exposed to thermal stress during its spawning cycle over the course of 5 weeks, during which time transcriptomic and polar metabolomic data were collected. We analyzed these data streams individually, and then integrated both data sets using MAGI (Metabolite Annotation and Gene Integration) to investigate molecular transitions and biochemical reactions. Results Our results reveal the complexity of the thermal stress phenome in M. capitata , which includes many genes involved in redox regulation, biomineralization, and reproduction. The size and number of modules in the gene co-expression networks expanded from the initial stress response to the onset of bleaching. The later stages involved the suppression of metabolite transport by the coral host, including a variety of sodium-coupled transporters and a putative ammonium transporter, possibly as a response to reduction in algal productivity. The gene-metabolite integration data suggest that thermal treatment results in the activation of animal redox stress pathways involved in quenching molecular oxygen to prevent an overabundance of reactive oxygen species. Lastly, evidence that thermal stress affects reproductive activity was provided by the downregulation of CYP-like genes and the irregular production of sex hormones during the mass spawning cycle. Overall, redox regulation and metabolite transport are key components of the coral animal thermal stress phenome. Mass spawning was highly attenuated under thermal stress, suggesting that global climate change may negatively impact reproductive behavior in this species. 

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