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1. The Arabidopsis gene co‐expression network

   https://doi.org/10.1002/pld3.396  

   Burks, David J.; Sengupta, Soham; De, Ronika; Mittler, Ron; Azad, Rajeev K. (April 2022, Plant Direct)

   Abstract Identifying genes that interact to confer a biological function to an organism is one of the main goals of functional genomics. High‐throughput technologies for assessment and quantification of genome‐wide gene expression patterns have enabled systems‐level analyses to infer pathways or networks of genes involved in different functions under many different conditions. Here, we leveraged the publicly available, information‐rich RNA‐Seq datasets of the model plantArabidopsis thalianato construct a gene co‐expression network, which was partitioned into clusters or modules that harbor genes correlated by expression. Gene ontology and pathway enrichment analyses were performed to assess functional terms and pathways that were enriched within the different gene modules. By interrogating the co‐expression network for genes in different modules that associate with a gene of interest, diverse functional roles of the gene can be deciphered. By mapping genes differentially expressing under a certain condition inArabidopsisonto the co‐expression network, we demonstrate the ability of the network to uncover novel genes that are likely transcriptionally active but prone to be missed by standard statistical approaches due to their falling outside of the confidence zone of detection. To our knowledge, this is the firstA. thalianaco‐expression network constructed using the entire mRNA‐Seq datasets (>20,000) available at the NCBI SRA database. The developed network can serve as a useful resource for theArabidopsisresearch community to interrogate specific genes of interest within the network, retrieve the respective interactomes, decipher gene modules that are transcriptionally altered under certain condition or stage, and gain understanding of gene functions. 

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2. The maize striate leaves2 ( sr2 ) gene encodes a conserved DUF3732 domain and is homologous to the rice yss1 gene

   https://doi.org/10.1002/pld3.567  

   Brady, Meghan J; Cheam, Maya; Gent, Jonathan I; Dawe, R Kelly (February 2024, Plant Direct)

   Abstract Maize striate leaves2(sr2) is a mutant that causes white stripes on leaves that has been used in mapping studies for decades though the underlying gene has not been identified. Thesr2locus has been previously mapped to small regions of normal chromosome 10 (N10) and a rearranged variant called abnormal chromosome 10 (Ab10). A comparison of assembled genomes carrying N10 and Ab10 revealed only five candidatesr2genes. Analysis of a stock carrying thesr2reference allele (sr2‐ref) showed that one of the five genes has a transposon insertion that disrupts its protein sequence and has a severe reduction in mRNA. An independent Mutator transposon insertion in the gene (sr2‐Mu) failed to complement thesr2‐refmutation, and plants homozygous forsr2‐Mushowed white striped leaf margins. Thesr2gene encodes a DUF3732 protein with strong homology to a rice gene with a similar mutant phenotype calledyoung seedling stripe1(yss1). These and other published data suggest thatsr2may have a function in plastid gene expression. 

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3. De Novo Gene Birth, Horizontal Gene Transfer, and Gene Duplication as Sources of New Gene Families Associated with the Origin of Symbiosis in Amanita

   https://doi.org/10.1093/gbe/evaa193  

   Wang, Yen-Wen; Hess, Jaqueline; Slot, Jason C; Pringle, Anne (November 2020, Genome Biology and Evolution)

   Ma, Li-Jun (Ed.)

   Abstract By introducing novel capacities and functions, new genes and gene families may play a crucial role in ecological transitions. Mechanisms generating new gene families include de novo gene birth, horizontal gene transfer, and neofunctionalization following a duplication event. The ectomycorrhizal (ECM) symbiosis is a ubiquitous mutualism and the association has evolved repeatedly and independently many times among the fungi, but the evolutionary dynamics enabling its emergence remain elusive. We developed a phylogenetic workflow to first understand if gene families unique to ECM Amanita fungi and absent from closely related asymbiotic species are functionally relevant to the symbiosis, and then to systematically infer their origins. We identified 109 gene families unique to ECM Amanita species. Genes belonging to unique gene families are under strong purifying selection and are upregulated during symbiosis, compared with genes of conserved or orphan gene families. The origins of seven of the unique gene families are strongly supported as either de novo gene birth (two gene families), horizontal gene transfer (four), or gene duplication (one). An additional 34 families appear new because of their selective retention within symbiotic species. Among the 109 unique gene families, the most upregulated gene in symbiotic cultures encodes a 1-aminocyclopropane-1-carboxylate deaminase, an enzyme capable of downregulating the synthesis of the plant hormone ethylene, a common negative regulator of plant-microbial mutualisms. 

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4. Inferring gene-pathway associations from consolidated transcriptome datasets: an interactive gene network explorer for Tetrahymena thermophila

   https://doi.org/10.1093/nargab/lqaf067  

   Bertagna, Michael A.; Bright, Lydia J.; Ye, Fei; Jiang, Yu-Yang; Sarkar, Debolina; Pradhan, Ajay; Kumar, Santosh; Gao, Shan; Turkewitz, Aaron P.; Tsypin, Lev M_Z (May 2025, NAR Genomics and Bioinformatics)

   Abstract Although an established model organism, Tetrahymena thermophila remains comparatively inaccessible to high throughput screens, and alternative bioinformatic approaches still rely on unconnected datasets and outdated algorithms. Here, we report a new approach to consolidating RNA-seq and microarray data based on a systematic exploration of parameters and computational controls, enabling us to infer functional gene associations from their co-expression patterns. To illustrate the power of this approach, we took advantage of new data regarding a previously studied pathway, the biogenesis of a secretory organelle called the mucocyst. Our untargeted clustering approach recovered over 80% of the genes that were previously verified to play a role in mucocyst biogenesis. Furthermore, we tested four new genes that we predicted to be mucocyst-associated based on their co-expression and found that knocking out each of them results in mucocyst secretion defects. We also found that our approach succeeds in clustering genes associated with several other cellular pathways that we evaluated based on prior literature. We present the Tetrahymena Gene Network Explorer (TGNE) as an interactive tool for genetic hypothesis generation and functional annotation in this organism and as a framework for building similar tools for other systems. 

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5. The Gene scb-1 Underlies Variation in Caenorhabditis elegans Chemotherapeutic Responses

   https://doi.org/10.1534/g3.120.401310  

   Evans, Kathryn S.; Andersen, Erik C. (May 2020, G3: Genes|Genomes|Genetics)

   Pleiotropy, the concept that a single gene controls multiple distinct traits, is prevalent in most organisms and has broad implications for medicine and agriculture. The identification of the molecular mechanisms underlying pleiotropy has the power to reveal previously unknown biological connections between seemingly unrelated traits. Additionally, the discovery of pleiotropic genes increases our understanding of both genetic and phenotypic complexity by characterizing novel gene functions. Quantitative trait locus (QTL) mapping has been used to identify several pleiotropic regions in many organisms. However, gene knockout studies are needed to eliminate the possibility of tightly linked, non-pleiotropic loci. Here, we use a panel of 296 recombinant inbred advanced intercross lines of Caenorhabditis elegans and a high-throughput fitness assay to identify a single large-effect QTL on the center of chromosome V associated with variation in responses to eight chemotherapeutics. We validate this QTL with near-isogenic lines and pair genome-wide gene expression data with drug response traits to perform mediation analysis, leading to the identification of a pleiotropic candidate gene, scb-1 for some of the eight chemotherapeutics. Using deletion strains created by genome editing, we show that scb-1 , which was previously implicated in response to bleomycin, also underlies responses to other double-strand DNA break-inducing chemotherapeutics. This finding provides new evidence for the role of scb-1 in the nematode drug response and highlights the power of mediation analysis to identify causal genes. 

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