Project description:BACKGROUND: Genomic prediction (GP) based on single nucleotide polymorphisms (SNP) has become a broadly used tool to increase the gain of selection in plant breeding. However, using predictors that are biologically closer to the phenotypes such as transcriptome and metabolome may increase the prediction ability in GP. The objectives of this study were to (i) assess the prediction ability for three phenotypic traits using different omic datasets including sequence variants (SV), deleterious SV (dSV), tolerant SV (tSV), expression presence/absence variation (ePAV), gene expression (GE), transcript expression (TE), and metabolites (M) as single predictors in comparison to those using a SNP array; (ii) investigate the improvement in prediction ability when combining multiple omic datasets information to predict phenotypic variation in barley breeding programs; (iii) explore the relationship between genes and metabolites to unravel the metabolic pathway of the three above mentioned phenotypic traits.RESULTS: The prediction ability from genomic best linear unbiased prediction (GBLUP) for the three traits using dSV information was higher than when using tSV, all SV information, or the SNP array. Any predictors from the transcriptome (GE, TE, as well as ePAV) and metabolome provided higher prediction abilities compared to the SNP array and SV on average across the three traits. In addition, some (di)-similarity existed between different omic datasets, and therefore provided complementary biological perspectives to phenotypic variation. Optimal combining the information of dSV, TE, ePAV, as well as metabolites into GP models could improve the prediction ability over that of the single predictors alone.CONCLUSIONS: The use of integrated omic datasets in GP model is highly recommended. Furthermore, we evaluated a cost-effective approach generating 3’end mRNA sequencing with transcriptome data extracted from seedling without losing prediction ability in comparison to the full-length mRNA sequencing, paving the path for the use of such prediction methods in commercial breeding programs.

Project description:A multi-omic approach in a clinical experimental study identified circulating biomarkers reflecting glucocorticoid exposure. Background: Endogenous glucocorticoids (GC) are mechanistically linked to common diseases and are important as drugs in the treatment of many disorders. There is no marker that can measure and quantify GC action. Our aim was to identify circulating biomarkers of GC action using a clinical experimental study. Methods: In a randomized, crossover, single-blind trial, subjects with primary adrenal insufficiency received intravenous hydrocortisone infusion in a circadian pattern (physiological GC exposure) or isotonic saline (GC withdrawal) over 22 hours. Samples were collected at 7 AM (end of infusion). Integrated multi-omic analysis was used because of the complexity in GC action and the low number of subjects. The transcriptome in peripheral blood mononuclear cells (PBMCs) and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions. Replication of the plasma miRNA findings was performed in three independent studies. Results: During GC withdrawal, overnight urinary cortisol and cortisone excretion were undetectable. Correlation and hypernetwork analyses identified a transcriptomic profile derived from PBMCs and adipose tissue predictive of GC exposure, and a multi-omic cluster predictive of GC exposure. From the circulating ‘omic data, decreased expression of plasma miR-122-5p was associated with increased GC exposure. This finding was reproduced in three independent studies. Conclusion: We developed a human experimental model for physiological GC exposure and withdrawal. The integrated multi-omic data identified circulating miRNAs and metabolites associated with GC-responsive genes. In independent studies, miR-122-5p was shown to be associated with GC exposure. Background: Endogenous glucocorticoids (GC) are mechanistically linked to common diseases and are important as drugs in the treatment of many disorders. There is no marker that can measure and quantify GC action. Our aim was to identify circulating biomarkers of GC action using a clinical experimental study.

Project description:Currently, the treatment and prevention of multiple sclerosis (MS) continue to encounter significant challenges. Mendelian randomization (MR) analysis has emerged as a crucial research method in the pursuit of new therapeutic strategies. Accordingly, we hypothesize that there exists a causal association between genetic variants of specific plasma proteins and MS through MR mechanisms, and that key therapeutic targets can be precisely identified by integrating multi-omics analytical approaches. In this study, we developed a comprehensive analytical framework aimed at identifying and validating potential therapeutic targets for MS. The framework commenced with a two-sample Mendelian randomization (MR) study utilizing two large plasma protein quantitative trait locus (pQTL) datasets. Building on this foundation, we performed Bayesian co-localization analysis of coding genes, followed by a full phenotype-wide association study (PheWAS) on the co-positive genes identified through both analytical methods. This approach allowed us to explore the functions of key genes and the mechanisms of co-morbidity associated with the disease. Subsequently, we integrated protein-protein interaction (PPI) network analysis, gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to facilitate drug prediction and molecular docking studies. This study conducted a systematic analysis between two large plasma pQTLs datasets and MS. In the MR analysis, the MR analysis of Icelandic plasma pQTLs and MS identified 88 positive plasma proteins, while the MR analysis of the UK Biobank database pQTLs and MS identified 122 positive plasma proteins. By comparison, uroporphyrinogen III synthase (UROS) and glutathione S-transferase theta 2B (GSTT2B) were found to be the positive proteins shared by the two datasets. After false discovery rate (FDR) correction, signal transducer and activator of transcription 3 (STAT3) was a significantly positive protein in the analysis of Icelandic plasma pQTLs. In the analysis of the UK Biobank database pQTLs, advanced glycosylation end product-specific receptor (AGER), allograft inflammatory factor 1 (AIF1), butyrophilin subfamily 1 member A1 (BTN1A1), cluster of differentiation 58 (CD58), desmoglein 4 (DSG4), ecotropic viral integration site 5 (EVI5), tumor necrosis factor (TNF), and tumor necrosis factor receptor superfamily member 14 (TNFRSF14) were significantly positive proteins. After Bonferroni correction, AGER, CD58, EVI5, and TNF remained significantly positive proteins in the analysis of the UK Biobank database pQTLs. In the Bayesian colocalization analysis, EVI5 (PPH4 = 0.9800), O-GlcNAcase (OGA) (PPH4 = 0.8569), and TNFRSF14 (PPH4 = 0.8904) were the common positive genes in the two analysis methods. In conclusion, EVI5, OGA, and TNFRSF14 may be potential therapeutic targets for MS. Through the comprehensive application of MR analysis and Bayesian colocalization analysis, we have successfully identified that EVI5, OGA, and TNFRSF14 may be key therapeutic targets for MS. These findings may provide a scientific basis for the development of novel immunotherapies, combination treatment regimens, or targeted intervention strategies.

			Action	DRS
	SRR29234469_1.fastq.gz	Fastqsanger.gz
	SRR29234469_2.fastq.gz	Fastqsanger.gz
	SRR29234470_1.fastq.gz	Fastqsanger.gz
	SRR29234470_2.fastq.gz	Fastqsanger.gz
	SRR29234471_1.fastq.gz	Fastqsanger.gz

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Multi-omic analysis identifies metabolic biomarkers for early detection of breast cancer and prediction of therapeutic responses

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