Computational identification of conserved microRNAs and functional annotation of their target genes in Citrus limon

AbstractBackgroundGenome-wide association and fine-mapping studies have enabled the discovery of single nucleotide polymorphisms (SNPs) and other variants that are significantly associated with many autoimmune diseases including type 1 diabetes (T1D). However, many of the SNPs lie in non-coding regions, limiting the identification of mechanisms that contribute to autoimmune disease progression.MethodsAutoimmunity results from a failure of immune tolerance, suggesting that regulatory T cells (Treg) are likely a significant point of impact for this genetic risk, as Treg are critical for immune tolerance. Focusing on T1D as a model of defective function of Treg in autoimmunity, we designed a SNPs filtering workflow called 3 Dimensional Functional Annotation of Accessible Cell Type Specific SNPs (3DFAACTS-SNP) that utilises overlapping profiles of Treg-specific epigenomic data (ATAC-seq, Hi-C and FOXP3-ChIP) to identify regulatory elements potentially driving the effect of variants associated with T1D, and the gene(s) that they control.ResultsUsing 3DFAACTS-SNP we identified 36 SNPs with plausible Treg-specific mechanisms of action contributing to T1D from 1,228 T1D fine-mapped variants, identifying 119 novel interacting regions resulting in the identification of 51 candidate target genes. We further demonstrated the utility of the workflow by applying it to three other fine-mapped/meta-analysed SNP autoimmune datasets, identifying 17 Treg-centric candidate variants and 35 interacting genes. Finally, we demonstrate the broad utility of 3DFAACTS-SNP for functional annotation of any genetic variation using all common (>10% allele frequency) variants from the Genome Aggregation Database (gnomAD). We identified 7,900 candidate variants and 3,245 candidate target genes, generating a list of potential sites for future T1D or autoimmune research.ConclusionsWe demonstrate that it is possible to further prioritise variants that contribute to T1D based on regulatory function and illustrate the power of using cell type specific multi-omics datasets to determine disease mechanisms. The 3DFAACTS-SNP workflow can be customised to any cell type for which the individual datasets for functional annotation have been generated, giving broad applicability and utility.

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Identification of a four-microRNA panel in serum as promising biomarker for colorectal carcinoma detection

Biomarkers in Medicine ◽

10.2217/bmm-2019-0605 ◽

2020 ◽

Vol 14 (9) ◽

pp. 749-760

Author(s):

Guocheng Huang ◽

Benlin Wei ◽

Zebo Chen ◽

Jingyao Wang ◽

Liwen Zhao ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Functional Annotation ◽

Target Genes ◽

Diagnostic Marker ◽

Area Under The Curve ◽

Serum Mirna ◽

Reverse Transcription Pcr ◽

Noninvasive Biomarker ◽

Diagnostic Panel ◽

Normal Controls

Background: Screening for colorectal carcinoma (CRC) lacks an efficient, inexpensive and noninvasive approach. The stable presence of serum miRNA is expected to become a new diagnostic marker. Materials & methods: Based on 135 CRC patients and 135 normal controls, this study was conducted in three phases to identify suitable serum miRNA for CRC diagnosis by using quantitative reverse transcription PCR. Bioinformatic assays were used for target genes prediction and functional annotation. Results: Serum expression level of seven miRNAs were significantly different between CRC patients and the normal controls. The final diagnostic panel (area under the curve = 0.893; sensitivity = 81.25%, specificity = 73.33%) consists of miR-203a-3p, miR-145-5p, miR-375-3p and miR-200c-3p. Conclusion: The four-miRNA panel may serve as a novel, noninvasive biomarker for CRC diagnosis and screening.

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Biological functional annotation of retinoic acid alpha and beta in mouse liver based on genome-wide binding

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00105.2014 ◽

2014 ◽

Vol 307 (2) ◽

pp. G205-G218 ◽

Cited By ~ 5

Author(s):

Yuqi He ◽

Jessica Tsuei ◽

Yu-Jui Yvonne Wan

Keyword(s):

Retinoic Acid ◽

Functional Annotation ◽

Mouse Liver ◽

Molecular Mechanisms ◽

Target Genes ◽

Biological Effects ◽

Control Group ◽

Receptor Isoforms ◽

Genome Wide ◽

Pathway Regulation

Retinoic acid (RA) has diverse biological effects. The liver stores vitamin A, generates RA, and expresses receptors for RA. The current study examines the hepatic binding profile of two RA receptor isoforms, RARA (RARα) and RARB (RARβ), in response to RA treatment in mouse livers. Our data uncovered 35,521, and 14,968 genomic bindings for RARA and RARB, respectively. Each expressed unique and common bindings, implying their redundant and specific roles. RARB has higher RA responsiveness than RARB. RA treatment generated 18,821 novel RARB bindings but only 14,798 of RARA bindings, compared with the control group. RAR frequently bound the consensus hormone response element [HRE; (A/G)G(G/T)TCA], which often contained the motifs assigned to SP1, GABPA, and FOXA2, suggesting potential interactions between those transcriptional factors. Functional annotation coupled with principle component analysis revealed that the function of RAR target genes were motif dependent. Taken together, the cistrome of RARA and RARB revealed their extensive biological roles in the mouse liver. RAR target genes are enriched in various biological processes. The hepatic RAR genome-wide binding data can help us understand the global molecular mechanisms underlying RAR and RA-mediated gene and pathway regulation.

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Expression analysis of miRNAs and their putative target genes confirm a preponderant role of transcription factors in the early response of oil palm plants to salinity stress

BMC Plant Biology ◽

10.1186/s12870-021-03296-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fernanda Ferreira Salgado ◽

Letícia Rios Vieira ◽

Vivianny Nayse Belo Silva ◽

André Pereira Leão ◽

Priscila Grynberg ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Salinity Stress ◽

Oil Palm ◽

Functional Annotation ◽

Target Genes ◽

Early Response ◽

Differentially Expressed ◽

Putative Target

Abstract Background Several mechanisms regulating gene expression contribute to restore and reestablish cellular homeostasis so that plants can adapt and survive in adverse situations. MicroRNAs (miRNAs) play roles important in the transcriptional and post-transcriptional regulation of gene expression, emerging as a regulatory molecule key in the responses to plant stress, such as cold, heat, drought, and salt. This work is a comprehensive and large-scale miRNA analysis performed to characterize the miRNA population present in oil palm (Elaeis guineensis Jacq.) exposed to a high level of salt stress, to identify miRNA-putative target genes in the oil palm genome, and to perform an in silico comparison of the expression profile of the miRNAs and their putative target genes. Results A group of 79 miRNAs was found in oil palm, been 52 known miRNAs and 27 new ones. The known miRNAs found belonged to 28 families. Those miRNAs led to 229 distinct miRNA-putative target genes identified in the genome of oil palm. miRNAs and putative target genes differentially expressed under salinity stress were then selected for functional annotation analysis. The regulation of transcription, DNA-templated, and the oxidation-reduction process were the biological processes with the highest number of hits to the putative target genes, while protein binding and DNA binding were the molecular functions with the highest number of hits. Finally, the nucleus was the cellular component with the highest number of hits. The functional annotation of the putative target genes differentially expressed under salinity stress showed several ones coding for transcription factors which have already proven able to result in tolerance to salinity stress by overexpression or knockout in other plant species. Conclusions Our findings provide new insights into the early response of young oil palm plants to salinity stress and confirm an expected preponderant role of transcription factors - such as NF-YA3, HOX32, and GRF1 - in this response. Besides, it points out potential salt-responsive miRNAs and miRNA-putative target genes that one can utilize to develop oil palm plants tolerant to salinity stress.

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Computational identification and characterization of conserved miRNAs and their putative target genes in Eclipta prostrata

Gene Reports ◽

10.1016/j.genrep.2018.03.020 ◽

2018 ◽

Vol 11 ◽

pp. 213-219 ◽

Cited By ~ 1

Author(s):

Souvagyalaxmi Sahoo ◽

Rashmi Rekha Samal ◽

Sangita Dixit

Keyword(s):

Target Genes ◽

Putative Target ◽

Eclipta Prostrata ◽

Computational Identification ◽

Identification And Characterization

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Computational identification of putative miRNAs and their target genes in pathogenic amoeba Naegleria fowleri

Bioinformation ◽

10.6026/97320630011550 ◽

2015 ◽

Vol 11 (12) ◽

pp. 550-557 ◽

Cited By ~ 1

Author(s):

Dyavegowda Padmashree ◽

◽

Narayana Swamy ◽

Keyword(s):

Target Genes ◽

Naegleria Fowleri ◽

Computational Identification ◽

Nægleria Fowleri

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Transcriptome Analysis Reveals Differentially Expressed Genes and Long Non-coding RNAs Associated With Fecundity in Sheep Hypothalamus With Different FecB Genotypes

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.633747 ◽

2021 ◽

Vol 9 ◽

Author(s):

Si Chen ◽

Xiaofei Guo ◽

Xiaoyun He ◽

Ran Di ◽

Xiaosheng Zhang ◽

...

Keyword(s):

Functional Annotation ◽

Target Genes ◽

Expression Profiles ◽

Regulatory Elements ◽

Reproductive Hormones ◽

Differentially Expressed ◽

Wild Type ◽

Reproductive Process ◽

Gnrh Secretion ◽

Non Coding Rnas

Small-tailed Han sheep, with different FecB genotypes, manifest distinct ovulation rates and fecundities, which are due to differences in reproductive hormones secreted by the hypothalamic–pituitary–ovarian axis. Nevertheless, the function of the hypothalamus against a FecB mutant background on increasing ovulation rate is rarely reported. Therefore, we determined the expression profiles of hypothalamus tissue collected from six wild-type (WW) and six FecB mutant homozygous (BB) ewes at the follicular and luteal phases by whole-transcriptome sequencing. We identified 53 differentially expressed mRNAs (DEGs) and 40 differentially expressed long non-coding RNAs (DELs) between the two estrus states. Functional annotation analysis revealed that one of the DEGs, PRL, was particularly enriched in the hypothalamic function, hormone-related, and reproductive pathways. The lncRNA–target gene interaction networks and KEGG analysis in combination suggest that the lncRNAs LINC-676 and WNT3-AS cis-acting on DRD2 and WNT9B in different phases may induce gonadotropin-releasing hormone (GnRH) secretion. Furthermore, there were differences of regulatory elements and WNT gene family members involved in the follicular–luteal transition in the reproductive process between wild-type (WNT7A) and FecB mutant sheep (WNT9B). We combined the DEG and DEL data sets screened from different estrus states and genotypes. The overlap of these two sets was identified to select the mRNAs and lncRNAs that have major effects on ovulation. Among the overlapping molecules, seven DEGs and four DELs were involved in the follicular–luteal transition regulated by FecB mutation. Functional annotation analysis showed that two DEGs (FKBP5 and KITLG) were enriched in melanogenesis, oxytocin, and GnRH secretion. LINC-219386 and IGF2-AS were highly expressed in the BB ewes compared with WW ewes, modulating their target genes (DMXL2 and IGF2) to produce more GnRH during follicular development, which explains why mutated ewes produced more mature follicles. These results from expression profiling of the hypothalamus with the FecB mutation at different estrus states provide new insights into how the hypothalamus regulates ovulation under the effect of the FecB mutation.

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