Integrated Omics Approach Research Articles

An Investigation of the Altered Textural Property in Woody Breast Myopathy Using an Integrative Omics Approach.

Woody breast (WB) is a myopathy observed in broiler Pectoralis major (PM) characterized by its tough and rubbery texture with greater level of calcium content. The objective of this study was to investigate the functionality/integrity of WB sarcoplasmic reticulum (SR), which may contribute to the elevated calcium content observed in WB and other factors that may influence WB texture. Fourteen Ross line broiler PM [7 severe WB and 7 normal (N)] were selected, packaged, and frozen at −20°C at 8 h postmortem from a commercial processing plant. Samples were used to measure pH, sarcomere length, proteolysis, calpain activity, collagenase activity, collagen content, collagen crosslinks density, and connective tissue peak transitional temperature. Exudate was also collected from each sample to evaluate free calcium concentration. The SR fraction of the samples was separated and utilized for proteomic and lipidomic analysis. The WB PM had a higher pH, shorter sarcomeres, lower % of intact troponin-T, more autolyzed μ/m calpain, more activated collagenase, greater collagen content, greater mature collagen crosslinks density, and higher connective tissue peak transitional temperature than the N PM (p ≤ 0.05). Exudate from WB PM had higher levels of free calcium than those from N PM (p < 0.05). Proteomics data revealed an upregulation of calcium transport proteins and a downregulation of proteins responsible for calcium release (p < 0.05) in WB SR. Interestingly, there was an upregulation of phospholipase A2 (PLA2), and cholinesterase exhibited a 7.6-fold increase in WB SR (p < 0.01). Lipidomics data revealed WB SR had less relative % of phosphatidylcholine (PC) and more lysophosphatidylcholine (LPC; p < 0.05). The results indicated that upregulation of calcium transport proteins and downregulation of calcium-release proteins in WB SR may be the muscle’s attempt to regulate this proposed excessive signaling of calcium release due to multiple factors, such as upregulation of PLA2 resulting in PC hydrolysis and presence of cholinesterase inhibitors in the system prolonging action potential. In addition, the textural abnormality of WB may be the combined effects of shorter sarcomere length and more collagen with greater crosslink density being deposited in the broiler PM.

Integrated Omics Approaches Revealed the Osmotic Stress-Responsive Genes and Microbiota in Gill of Marine Medaka.

ABSTRACTAquatic fishes face osmotic stress continuously, and the gill is the first tissue that senses and responds to the external osmotic challenges. However, the understandings of how the gill microbiota could respond to osmotic stress and their potential host-bacterium relationships are limited. The objectives of the current study are to identify the hypotonic responsive genes in the gill cells and profile the gill microbiota communities after fresh water transfer experiment via transcriptome sequencing and 16S rRNA gene sequencing. Transcriptome sequencing identified 1,034 differentially expressed genes (DEGs), such as aquaporin and sodium potassium chloride cotransporter, after the fresh water transfer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis further highlighted the steroid biosynthesis and glycosaminoglycan biosynthesis pathways in the gill. Moreover, the 16S rRNA gene sequencing identified Vibrio as the dominant bacterium in the seawater, which changed to Pseudomonas and Cetobacterium after the fresh water transfer. The alpha diversity analysis suggested that the gill bacterial diversity was lower in the fresh water transferred group. The KEGG and MetaCyc analysis further predicted the alteration of the glycosaminoglycan and chitin metabolisms in the gill bacteria. Collectively, the common glycosaminoglycan and chitin pathways in both the gill cells and gill microbiota suggest the host-bacterium interaction in gill facilitates the fresh water acclimation.IMPORTANCE This is the first study using the transcriptome and 16S rRNA gene sequencing to report the hypotonic responsive genes in gill cells and the compositions of gill microbiota in marine medaka. The overlapped glycosaminoglycan- and chitin-related pathways suggest host-bacterium interaction in fish gill during osmotic stress.

Omics approaches in bioremediation of environmental contaminants: An integrated approach for environmental safety and sustainability

Non-degradable pollutants have emerged as a result of industrialization, population growth, and lifestyle changes, endangering human health and the environment. Bioremediation is the process of clearing hazardous contaminants with the help of microorganisms, and cost-effective approach. The low-cost and environmentally acceptable approach to removing environmental pollutants from ecosystems is microbial bioremediation. However, to execute these different bioremediation approaches successfully, this is imperative to have a complete understanding of the variables impacting the development, metabolism, dynamics, and native microbial communities' activity in polluted areas. The emergence of new technologies like next-generation sequencing, protein and metabolic profiling, and advanced bioinformatic tools have provided critical insights into microbial communities and underlying mechanisms in environmental contaminant bioremediation. These omics approaches are meta-genomics, meta-transcriptomics, meta-proteomics, and metabolomics. Moreover, the advancements in these technologies have greatly aided in determining the effectiveness and implementing microbiological bioremediation approaches. At Environmental Protection Agency (EPA)-The government placed special emphasis on exploring how molecular and “omic” technologies may be used to determine the nature, behavior, and functions of the intrinsic microbial communities present at pollution containment systems. Several omics techniques are unquestionably more informative and valuable in elucidating the mechanism of the process and identifying the essential player's involved enzymes and their regulatory elements. This review provides an overview and description of the omics platforms that have been described in recent reports on omics approaches in bioremediation and that demonstrate the effectiveness of integrated omics approaches and their novel future use.

Gene Regulatory Circuits in Innate and Adaptive Immune Cells.

Cell identity and function largely rely on the programming of transcriptomes during development and differentiation. Signature gene expression programs are orchestrated by regulatory circuits consisting of cis-acting promoters and enhancers, which respond to a plethora of cues via the action of transcription factors. In turn, transcription factors direct epigenetic modifications to revise chromatin landscapes, and drive contacts between distal promoter-enhancer combinations. In immune cells, regulatory circuits for effector genes are especially complex and flexible, utilizing distinct sets of transcription factors and enhancers, depending on the cues each cell type receives during an infection, after sensing cellular damage, or upon encountering a tumor. Here, we review major players in the coordination of gene regulatory programs within innate and adaptive immune cells, as well as integrative omics approaches that can be leveraged to decipher their underlying circuitry.

Systematic Characterization of the Group 2 House Dust Mite Allergen in Dermatophagoides microceras.

BackgroundAllergic asthma, a chronic airway inflammatory disease, is a critical public health problem. Indoor house dust mites (HDMs) could cause allergic asthma. The prevalence of sensitization to Dermatophagoides microceras (Der m) was approximately 80% and is related to the immunoglobulin E crossing-reactivity of mites belonging to the same genus, Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farina (Der f). However, studies on Der m are scant.MethodsWe used integrated OMICs approaches to identify and characterize the group 2 mite allergen-like protein in Der m (Der m 2). We established a Der m 2-induced allergic asthma mouse model and treated the mice with a fungal immunomodulatory protein (FIP-fve) isolated from Flammulina veluptipes to evaluate the allergenicity of Der m 2 and the immunomodulatory effects of FIP-fve.ResultsBy performing de novo draft genome assembly and comparative genome analysis, we identified the putative 144-amino acid Der m 2 in silico and further confirmed its existence through liquid chromatography–tandem mass spectrometry. Der m 2 is a lipopolysaccharides (LPS)-binding protein. Thus, we examined the LPS-binding activity of recombinant Der m 2 by performing molecular docking analysis, co-immunoprecipitation (Co-IP), and a pull-down assay. Der m 2 elicited the production of pro-inflammatory cytokines, interleukin (IL)-6, and IL-8 in BEAS-2B cells, a human bronchial epithelial cell line, and induced airway hyperresponsiveness in mice. Furthermore, in mice sensitized with Der m 2, the administration of FIP-fve in either the earlier stage or the late stage, FIP-fve alleviated allergic asthma by moderating airway inflammation and remodeling.Conclusions Der m 2 induced inflammatory responses in cell and mouse models. FIP-fve alleviated inflammation in Der m 2-induced asthma in mice by exerting an immunomodulatory effect.

Integrative omics approaches for biosynthetic pathway discovery in plants.

Covering: up to 2022With the emergence of large amounts of omics data, computational approaches for the identification of plant natural product biosynthetic pathways and their genetic regulation have become increasingly important. While genomes provide clues regarding functional associations between genes based on gene clustering, metabolome mining provides a foundational technology to chart natural product structural diversity in plants, and transcriptomics has been successfully used to identify new members of their biosynthetic pathways based on coexpression. Thus far, most approaches utilizing transcriptomics and metabolomics have been targeted towards specific pathways and use one type of omics data at a time. Recent technological advances now provide new opportunities for integration of multiple omics types and untargeted pathway discovery. Here, we review advances in plant biosynthetic pathway discovery using genomics, transcriptomics, and metabolomics, as well as recent efforts towards omics integration. We highlight how transcriptomics and metabolomics provide complementary information to link genes to metabolites, by associating temporal and spatial gene expression levels with metabolite abundance levels across samples, and by matching mass-spectral features to enzyme families. Furthermore, we suggest that elucidation of gene regulatory networks using time-series data may prove useful for efforts to unwire the complexities of biosynthetic pathway components based on regulatory interactions and events.

Omics Technologies to Enhance Plant Based Functional Foods: An Overview.

Functional foods are natural products of plants that have health benefits beyond necessary nutrition. Functional foods are abundant in fruits, vegetables, spices, beverages and some are found in cereals, millets, pulses and oilseeds. Efforts to identify functional foods in our diet and their beneficial aspects are limited to few crops. Advances in sequencing and availability of different omics technologies have given opportunity to utilize these tools to enhance the functional components of the foods, thus ensuring the nutritional security. Integrated omics approaches including genomics, transcriptomics, proteomics, metabolomics coupled with artificial intelligence and machine learning approaches can be used to improve the crops. This review provides insights into omics studies that are carried out to find the active components and crop improvement by enhancing the functional compounds in different plants including cereals, millets, pulses, oilseeds, fruits, vegetables, spices, beverages and medicinal plants. There is a need to characterize functional foods that are being used in traditional medicines, as well as utilization of this knowledge to improve the staple foods in order to tackle malnutrition and hunger more effectively.

Mitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation.

Galactic cosmic rays are primarily composed of protons (85%), helium (14%), and high charge/high energy ions (HZEs) such as 56Fe, 28Si, and 16O. HZE exposure is a major risk factor for astronauts during deep-space travel due to the possibility of HZE-induced cancer. A systems biology integrated omics approach encompassing transcriptomics, proteomics, lipidomics, and functional biochemical assays was used to identify microenvironmental changes induced by HZE exposure. C57BL/6 mice were placed into six treatment groups and received the following irradiation treatments: 600 MeV/n 56Fe (0.2 Gy), 1 GeV/n 16O (0.2 Gy), 350 MeV/n 28Si (0.2 Gy), 137Cs (1.0 Gy) gamma rays, 137Cs (3.0 Gy) gamma rays, and sham irradiation. Left liver lobes were collected at 30, 60, 120, 270, and 360 days post-irradiation. Analysis of transcriptomic and proteomic data utilizing ingenuity pathway analysis identified multiple pathways involved in mitochondrial function that were altered after HZE irradiation. Lipids also exhibited changes that were linked to mitochondrial function. Molecular assays for mitochondrial Complex I activity showed significant decreases in activity after HZE exposure. HZE-induced mitochondrial dysfunction suggests an increased risk for deep space travel. Microenvironmental and pathway analysis as performed in this research identified possible targets for countermeasures to mitigate risk.

Top Trends in Multiomics Research: Evaluation of 52 Published Studies and New Ways of Thinking Terminology and Visual Displays.

Multiomics study designs have significantly increased understanding of complex biological systems. The multiomics literature is rapidly expanding and so is their heterogeneity. However, the intricacy and fragmentation of omics data are impeding further research. To examine current trends in multiomics field, we reviewed 52 articles from PubMed and Web of Science, which used an integrated omics approach, published between March 2006 and January 2021. From studies, data regarding investigated loci, species, omics type, and phenotype were extracted, curated, and streamlined according to standardized terminology, and summarized in a previously developed graphical summary. Evaluated studies included 21 omics types or applications of omics technology such as genomics, transcriptomics, metabolomics, epigenomics, environmental omics, and pharmacogenomics, species of various phyla including human, mouse, Arabidopsis thaliana, Saccharomyces cerevisiae, and various phenotypes, including cancer and COVID-19. In the analyzed studies, diverse methods, protocols, results, and terminology were used and accordingly, assessment of the studies was challenging. Adoption of standardized multiomics data presentation in the future will further buttress standardization of terminology and reporting of results in systems science. This shall catalyze, we suggest, innovation in both science communication and laboratory medicine by making available scientific knowledge that is easier to grasp, share, and harness toward medical breakthroughs.

Analysis of Nanotoxicity with Integrated Omics and Mechanobiology.

Nanoparticles (NPs) in biomedical applications have benefits owing to their small size. However, their intricate and sensitive nature makes an evaluation of the adverse effects of NPs on health necessary and challenging. Since there are limitations to conventional toxicological methods and omics analyses provide a more comprehensive molecular profiling of multifactorial biological systems, omics approaches are necessary to evaluate nanotoxicity. Compared to a single omics layer, integrated omics across multiple omics layers provides more sensitive and comprehensive details on NP-induced toxicity based on network integration analysis. As multi-omics data are heterogeneous and massive, computational methods such as machine learning (ML) have been applied for investigating correlation among each omics. This integration of omics and ML approaches will be helpful for analyzing nanotoxicity. To that end, mechanobiology has been applied for evaluating the biophysical changes in NPs by measuring the traction force and rigidity sensing in NP-treated cells using a sub-elastomeric pillar. Therefore, integrated omics approaches are suitable for elucidating mechanobiological effects exerted by NPs. These technologies will be valuable for expanding the safety evaluations of NPs. Here, we review the integration of omics, ML, and mechanobiology for evaluating nanotoxicity.

Integrated omics approaches for deciphering antifungal metabolites produced by a novel Bacillus species, B. cabrialesii TE3T, against the spot blotch disease of wheat (Triticum turgidum L. subsp. durum)

Bipolaris sorokiniana is an important biotic constraint for global wheat production, causing spot blotch disease. In this work, we present a comprehensive characterization of the cell-free culture filtrate (CF) and precipitated fraction (PF) of Bacillus cabrialesii TE3T showing an effective inhibition of spot blotch. Our results indicated that CF produced by B. cabrialesii TE3T inhibits the growth of B. sorokiniana through stable metabolites (after autoclaving and proteinase K treatment). Antifungal metabolites in CF and PF were explored by an integrated genomic-metabolomic approach. Genome-mining revealed that strain TE3T contains the biosynthetic potential to produce wide spectrum antifungal (surfactin, fengycin, and rhizocticin A) and antibacterial metabolites (bacillaene, bacilysin, bacillibactin, and subtilosin A), and through bioactivity-guided LC-ESI-MS/MS approach we determined that a lipopeptide complex of surfactin and fengycin homologs was responsible for antifungal activity exhibited by B. cabrialesii TE3T against the studied phytopathogen. In addition, our results demonstrate that i) a lipopeptide complex inhibits B. sorokiniana by disrupting its cytoplasmatic membrane and ii) reduced spot blotch disease by 93 %. These findings show the potential application of metabolites produced by strain TE3T against B. sorokiniana and provide the first insight into antifungal metabolites produced by the novel Bacillus species, Bacillus cabrialesii.

Integrated Omics Reveals the Orchestrating Role of Calycosin in Danggui Buxue Tang, a Herbal Formula Containing Angelicae Sinensis Radix and Astragali Radix, in Inducing Osteoblastic Differentiation and Proliferation.

Systems biology unravels the black box of signaling pathway of cells; but which has not been extensively applied to reveal the mechanistic synergy of a herbal formula. The therapeutic efficacies of a herbal formula having multi-target, multi-function and multi-pathway are the niches of traditional Chinese medicine (TCM). Here, we reported an integrated omics approach, coupled with the knockout of an active compound, to measure the regulation of cellular signaling, as to reveal the landscape in cultured rat osteoblasts having synergistic pharmacological efficacy of Danggui Buxue Tang (DBT), a Chinese herbal formula containing Angelicae Sinensis Radix and Astragali Radix. The changes in signaling pathways responsible for energy metabolism, RNA metabolism and protein metabolism showed distinct features between DBT and calycosin-depleted DBT. Here, our results show that calycosin within DBT can orchestrate the osteoblastic functions and signaling pathways of the entire herbal formula. This finding reveals the harmony of herbal medicine in pharmacological functions, as well as the design of drug/herbal medicine formulation. The integration of systems biology can provide novel and essential insights into the synergistic property of a herbal formula, which is a key in modernizing TCM.

Evaluation of the Relationships Between Microbiota and Metabolites in Soft-Type Ripened Cheese Using an Integrated Omics Approach.

Cheese ripening is effected by various microorganisms and results in the characteristic flavors of cheese. Owing to the complexity of the microbiota involved, the relationship between microorganisms and components during ripening remains unclear. In this study, metagenomics and metabolomics were integrated to reveal these relationships in three kinds of surface mold-ripened cheeses and two kinds of bacterial smear-ripened cheeses. The microbiota is broadly divided into two groups to correspond with different cheese types. Furthermore, surface mold-ripened cheese showed similar microbiota regardless of the cheese variety, whereas bacterial smear-ripened cheese showed specific microbiota characterized by marine bacteria (MB) and halophilic and alkaliphilic lactic acid bacteria for each cheese variety. In the metabolite analysis, volatile compounds suggested differences in cheese types, although organic acids and free amino acids could not determine the cheese characteristics. On the other hand, Spearman correlation analysis revealed that the abundance of specific bacteria was related to the formation of specific organic acids, free amino acids, and volatile compounds. In particular, MB was positively correlated with esters and pyrazines, indicating their contribution to cheese quality. These methodologies and results further our understanding of microorganisms and allow us to select useful strains for cheese ripening.

Genetic Improvement in Sunflower Breeding—Integrated Omics Approach

Foresight in climate change and the challenges ahead requires a systematic approach to sunflower breeding that will encompass all available technologies. There is a great scarcity of desirable genetic variation, which is in fact undiscovered because it has not been sufficiently researched as detection and designing favorable genetic variation largely depends on thorough genome sequencing through broad and deep resequencing. Basic exploration of genomes is insufficient to find insight about important physiological and molecular mechanisms unique to crops. That is why integrating information from genomics, epigenomics, transcriptomics, proteomics, metabolomics and phenomics enables a comprehensive understanding of the molecular mechanisms in the background of architecture of many important quantitative traits. Omics technologies offer novel possibilities for deciphering the complex pathways and molecular profiling through the level of systems biology and can provide important answers that can be utilized for more efficient breeding of sunflower. In this review, we present omics profiling approaches in order to address their possibilities and usefulness as a potential breeding tools in sunflower genetic improvement.

Microbial enrichment and meta-omics analysis identify CAZymes from mangrove sediments with unique properties

Although lignocellulose is the most abundant and renewable natural resource for biofuel production, its use remains under exploration because of its highly recalcitrant structure. Its deconstruction into sugar monomers is mainly driven by carbohydrate-active enzymes (CAZymes). To develop highly efficient and fast strategies to discover biomass-degrading enzymes for biorefinery applications, an enrichment process combined with integrative omics approaches was used to identify new CAZymes. The lignocellulolytic-enriched mangrove microbial community (LignoManG) established on sugarcane bagasse (SB) was enriched with lignocellulolytic bacteria and fungi such as Proteobacteria, Bacteroidetes, Basidiomycota, and Ascomycota. These microbial communities were able to degrade up to 55 % of the total SB, indicating the production of lignocellulolytic enzymes. Metagenomic analysis revealed that the LignoManG harbors 18.042 CAZyme sequences such as of cellulases, hemicellulases, carbohydrate esterases, and lytic polysaccharide monooxygenase. Similarly, our metaproteomic analysis depicted several enzymes from distinct families of different CAZy families. Based on the LignoManG data, a xylanase (coldXynZ) was selected, amplified, cloned, expressed, and biochemically characterized. The enzyme displayed psicrofilic properties, with the highest activity at 15 °C, retaining 77 % of its activity when incubated at 0 °C. Moreover, molecular modeling in silico indicated that coldXynZ is composed of a TIM barrel, which is a typical folding found in the GH10 family, and displayed similar structural features related to cold-adapted enzymes. Collectively, the data generated in this study represent a valuable resource for lignocellulolytic enzymes with potential biotechnological applications.

1. An Integrative Omics Approach to Drug Discovery

1. An Integrative Omics Approach to Drug Discovery

Zebrafish as the toxicant screening model: Transgenic and omics approaches.

The production of large amounts of synthetic industrial and biomedical compounds, together with environmental pollutants, poses a risk to our ecosystem and induces negative effects on the health of wildlife and human beings. With the emergence of the global problem of chemical contamination, the adverse biological effects of these chemicals are gaining attention among the scientific communities, industry, governments, and the public. Among these chemicals, endocrine disrupting chemicals (EDCs) are regarded as one of the major global issues that potentially affecting our health. There is an urgent need of understanding the potential hazards of such chemicals. Zebrafish have been widely used in the aquatic toxicology. In this review, we first discuss the strategy of transgenic lines that used in the toxicological studies, followed by summarizing the current omics approaches (transcriptomics, proteomics, metabolomics, and epigenomics) on toxicities of EDCs in this model. We will also discuss the possible transgenerational effects in zebrafish and future prospective of the integrated omics approaches with customized transgenic organism. To conclude, we summarize the current findings in the field, and provide our opinions on future environmental toxicity research in the zebrafish model.

Plant sugars: Homeostasis and transport under abiotic stress in plants.

The sessile nature of plants' life is endowed with a highly evolved defense system to adapt and survive under environmental extremes. To combat such stresses, plants have developed complex and well-coordinated molecular and metabolic networks encompassing genes, metabolites, and acclimation responses. These modulate growth, photosynthesis, osmotic maintenance, and carbohydrate homeostasis. Under a given stress condition, sugars act as key players in stress perception, signaling, and are a regulatory hub for stress-mediated gene expression ensuring responses of osmotic adjustment, scavenging of reactive oxygen species, and maintaining the cellular energy status through carbon partitioning. Several sugar transporters are known to regulate carbohydrate partitioning and key signal transduction steps involved in the perception of biotic and abiotic stresses. Sugar transporters such as SUGARS WILL EVENTUALLY BE EXPORTED TRANSPORTER (SWEETs), SUCROSE TRANSPORTERS (SUTs), and MONOSACCHARIDE TRANSPORTERS (MSTs) are involved in sugar loading and unloading as well as long-distance transport (source to sink) besides orchestrating oxidative and osmotic stress tolerance. It is thus necessary to understand the structure-function relationship of these sugar transporters to fine-tune the abiotic stress-modulated responses. Advances in genomics have unraveled many sugars signaling components playing a key role in cross-talk in abiotic stress pathways. An integrated omics approach may aid in the identification and characterization of sugar transporters that could become targets for developing stress tolerance plants to mitigate climate change effects and improve crop yield. In this review, we have presented an up-to-date analysis of the sugar homeostasis under abiotic stresses as well as describe the structure and functions of sugar transporters under abiotic stresses.

Elucidation of enzymes involved in the biosynthetic pathway of bioactive polyacetylenes in Bidens pilosa using integrated omics approaches.

Polyacetylene compounds from Bidens pilosa are known to have several pharmacological activities. In this study, we identified major genes encoding enzymes involved in the biosynthesis of polyacetylene in B. pilosa. Seven polyacetylene metabolites present in B. pilosa leaves were induced by methyl jasmonate (MeJA) treatment and physical wounding. Transcriptome analysis via high-throughput sequencing revealed 39 202 annotated gene fragment sequences. A DNA microarray established by the 39 202 annotated genes was used to profile gene expression in B. pilosa leaf and root tissues. As no polyacetylene compounds were found in roots, the gene expression pattern in root tissue was used as a negative control. By subtracting MeJA-induced genes in roots, we obtained 1216 genes in leaves showing an approximate three-fold increase in expression post-MeJA treatment. Nine genes encoding enzymes with desaturation function were selected for confirmation of expression by qRT-PCR. Among them, two genes, BPTC030748 and BPTC012564, were predicted to encode Δ12-oleate desaturase (OD) and Δ12-fatty acid acetylenase (FAA), respectively. In B. pilosa leaves, RNAi knock-down concomitantly decreased, while virus-mediated transient overexpression of either gene elevated polyacetylene content. In summary, we demonstrate that two important enzymes, Δ12-oleate desaturase and Δ12-fatty acid acetylenase, involved in desaturation of linear fatty acid precursors play a role in polyacetylene biosynthesis in an important medicinal plant, Bidens pilosa.

Integrated omics unveil the secondary metabolic landscape of a basal dinoflagellate

BackgroundSome dinoflagellates cause harmful algal blooms, releasing toxic secondary metabolites, to the detriment of marine ecosystems and human health. Our understanding of dinoflagellate toxin biosynthesis has been hampered by their unusually large genomes. To overcome this challenge, for the first time, we sequenced the genome, microRNAs, and mRNA isoforms of a basal dinoflagellate, Amphidinium gibbosum, and employed an integrated omics approach to understand its secondary metabolite biosynthesis.ResultsWe assembled the ~ 6.4-Gb A. gibbosum genome, and by probing decoded dinoflagellate genomes and transcriptomes, we identified the non-ribosomal peptide synthetase adenylation domain as essential for generation of specialized metabolites. Upon starving the cells of phosphate and nitrogen, we observed pronounced shifts in metabolite biosynthesis, suggestive of post-transcriptional regulation by microRNAs. Using Iso-Seq and RNA-seq data, we found that alternative splicing and polycistronic expression generate different transcripts for secondary metabolism.ConclusionsOur genomic findings suggest intricate integration of various metabolic enzymes that function iteratively to synthesize metabolites, providing mechanistic insights into how dinoflagellates synthesize secondary metabolites, depending upon nutrient availability. This study provides insights into toxin production associated with dinoflagellate blooms. The genome of this basal dinoflagellate provides important clues about dinoflagellate evolution and overcomes the large genome size, which has been a challenge previously.