Peer Review #1 of "Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis (v0.1)"

BackgroundThe involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein–protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease.MethodsGene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed. Differentially expressed genes which determined only in CSF (MSvs.control) and PBMCs (relapsevs.remission) separately integrated with PPI data to construct the Query-Query PPI (QQPPI) networks. The networks were further analyzed to investigate more central genes, functional modules and complexes involved in MS progression.ResultsThe networks were analyzed and high centrality genes were identified. Exploration of functional modules and complexes showed that the majority of high centrality genes incorporated in biological pathways driving MS pathogenesis. Proteasome and spliceosome were also noticeable in enriched pathways in PBMCs (relapsevs.remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MSvs.control) and CDC37, MAP3K3, MYC genes in PBMCs (relapsevs.remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways.DiscussionThis study showed that network-based analysis could explicate the complex interplay between biological processes underlying MS. Furthermore, an experimental validation of candidate genes can lead to identification of potential therapeutic targets.

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Identifying Candidate Genes for Hypoxia Adaptation of Tibet Chicken Embryos by Selection Signature Analyses and RNA Sequencing

Genes ◽

10.3390/genes11070823 ◽

2020 ◽

Vol 11 (7) ◽

pp. 823

Author(s):

Xiayi Liu ◽

Xiaochen Wang ◽

Jing Liu ◽

Xiangyu Wang ◽

Haigang Bao

Keyword(s):

Candidate Genes ◽

Rna Sequencing ◽

Differentially Expressed Genes ◽

Gallus Gallus ◽

Differentially Expressed ◽

Tibet Plateau ◽

Embryonic Liver ◽

Selection Signature ◽

Chicken Embryos ◽

Hypoxia Adaptation

The Tibet chicken (Gallus gallus) lives on the Qinghai–Tibet Plateau and adapts to the hypoxic environment very well. The objectives of this study was to obtain candidate genes associated with hypoxia adaptation in the Tibet chicken embryos. In the present study, we used the fixation index (Fst) and cross population extended haplotype homozygosity (XPEHH) statistical methods to detect signatures of positive selection of the Tibet chicken, and analyzed the RNA sequencing data from the embryonic liver and heart with HISAT, StringTie and Ballgown for differentially expressed genes between the Tibet chicken and White leghorn (Gallus gallus, a kind of lowland chicken) embryos hatched under hypoxia condition. Genes which were screened out by both selection signature analysis and RNA sequencing analysis could be regarded as candidate genes for hypoxia adaptation of chicken embryos. We screened out 1772 genes by XPEHH and 601 genes by Fst, and obtained 384 and 353 differentially expressed genes in embryonic liver and heart, respectively. Among these genes, 89 genes were considered as candidate genes for hypoxia adaptation in chicken embryos. ARNT, AHR, GSTK1 and FGFR1 could be considered the most important candidate genes. Our findings provide references to elucidate the molecular mechanism of hypoxia adaptation in Tibet chicken embryos.

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Differentially expressed genes in preimplantation human embryos: potential candidate genes for blastocyst formation and implantation

Journal of Assisted Reproduction and Genetics ◽

10.1007/s10815-016-0745-x ◽

2016 ◽

Vol 33 (8) ◽

pp. 1017-1025 ◽

Cited By ~ 9

Author(s):

Erika M. Munch ◽

Amy E. Sparks ◽

Jesus Gonzalez Bosquet ◽

Lane K. Christenson ◽

Eric J. Devor ◽

...

Keyword(s):

Candidate Genes ◽

Differentially Expressed Genes ◽

Differentially Expressed ◽

Human Embryos ◽

Potential Candidate ◽

Blastocyst Formation

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Identification and characterization of differentially expressed genes in Caenorhabditis elegans in response to pathogenic and nonpathogenic Stenotrophomonas maltophilia

10.21203/rs.2.14106/v2 ◽

2019 ◽

Author(s):

Leah J Radeke ◽

Michael Herman

Keyword(s):

Candidate Genes ◽

Differentially Expressed Genes ◽

Stenotrophomonas Maltophilia ◽

Defense Mechanisms ◽

Virulent Strain ◽

Differentially Expressed ◽

Transcriptional Responses ◽

Transcriptomic Response ◽

C Elegans ◽

Realistic Interaction

Abstract Background: Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes infection in immunocompromised patients. S. maltophilia isolates are genetically diverse, contain diverse virulence factors, and are variably pathogenic within several host species. Members of the Stenotrophomonas genus are part of the native microbiome of C. elegans , being found in greater relative abundance within the worm than its environment, suggesting that these bacteria accumulate within C. elegans . Thus, study of the C. elegans-Stenotrophomonas interaction is of both medical and ecological significance. To identify host defense mechanisms, we analyzed the C. elegans transcriptomic response to S. maltophilia strains of varying pathogenicity: K279a, an avirulent clinical isolate, JCMS, a virulent strain isolated in association with soil nematodes near Manhattan, KS, and JV3, an even more virulent environmental isolate. Results: Overall, we found 145 genes that are commonly differentially expressed in response to pathogenic S. maltophilia strains, 89% of which are upregulated, with many even further upregulated in response to JV3 as compared to JCMS. There are many more JV3-specific differentially expressed genes (225, 11% upregulated) than JCMS-specific differentially expressed genes (14, 86% upregulated), suggesting JV3 has unique pathogenic mechanisms that could explain its increased virulence. We used connectivity within a gene network model to choose pathogen-specific and strain-specific differentially expressed candidate genes for functional analysis. Mutations in 13 of 22 candidate genes caused significant differences in C. elegans survival in response to at least one S. maltophilia strain, although not always the strain that induced differential expression, suggesting a dynamic response to varying levels of pathogenicity. Conclusions: Variation in observed pathogenicity and differences in host transcriptional responses to S. maltophilia strains reveal that strain-specific mechanisms play important roles in S. maltophilia pathogenesis. Furthermore, utilizing bacteria closely related to strains found in C. elegans natural environment provides a more realistic interaction for understanding host-pathogen response.

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Integrated metabolomic and transcriptomic analysis of the anthocyanin regulatory networks in Salvia miltiorrhiza Bge. flowers

10.21203/rs.3.rs-25292/v1 ◽

2020 ◽

Author(s):

Tao Jiang ◽

Meide Zhang ◽

Chunxiu Wen ◽

Xiaoliang Xie ◽

Wei Tian ◽

...

Keyword(s):

Candidate Genes ◽

Differentially Expressed Genes ◽

Regulatory Networks ◽

Anthocyanin Biosynthesis ◽

Salvia Miltiorrhiza ◽

Flower Color ◽

Differentially Expressed ◽

Integrated Analysis ◽

Anthocyanin Content ◽

Transcriptomics Data

Abstract Background: The study objectives were to reveal the anthocyanin biosynthesis metabolic pathway in white and purple flowers of Salvia miltiorrhiza using metabolomics and transcriptomics, to identify different anthocyanin metabolites, and to analyze the differentially expressed genes involved in anthocyanin biosynthesis . Results: We analyzed the metabolomics and transcriptomics data of Salvia miltiorrhiza flowers. A total of 1994 differentially expressed genes and 84 flavonoid metabolites were identified between the white and purple flowers of Salvia miltiorrhiza . Integrated analysis of transcriptomic and metabolomics showed that cyanidin 3,5-O-diglucoside, malvidin 3,5-diglucoside, and cyanidin 3-O-galactoside were mainly responsible for the purple flower color of Salvia miltiorrhiza. A total of 100 unigenes encoding 10 enzymes were identified as candidate genes involved in anthocyanin biosynthesis in Salvia miltiorrhiza flowers. The low expression of the ANS gene decreased the anthocyanin content but enhanced the accumulation of flavonoids in Salvia miltiorrhiza flowers. Conclusions: Our results provide valuable information on the anthocyanin metabolites and the candidate genes involved in the anthocyanin biosynthesis pathways in Salvia miltiorrhiza .

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Analysis of BMP15-Induced Transcriptome in Human Granulosa Cells for the Identification of Novel Candidate Genes for Primary Ovarian Insufficiency

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1553 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A763-A764

Author(s):

Raffaella Rossetti ◽

Marco Fornili ◽

Silvia Moleri ◽

Ilaria Ferrari ◽

Davide Gentilini ◽

...

Keyword(s):

Candidate Genes ◽

Differentially Expressed Genes ◽

Granulosa Cells ◽

Transcriptome Analysis ◽

Primary Ovarian Insufficiency ◽

Differentially Expressed ◽

Incomplete Penetrance ◽

Sequencing Analysis ◽

Ovarian Insufficiency ◽

Human Granulosa Cells

Abstract Primary Ovarian Insufficiency (POI) is a female fertility disorder which affects 1% of women before 40 years of age and manifests with amenorrhea, elevation of serum gonadotrophins and low estrogens. POI has a strong genetic component with incomplete penetrance. Several candidate genes have been described so far, however, its etiopathogenesis is mostly unknown. In order to discover the POI-related causative mechanisms, microarray transcriptome analysis in human granulosa cells (hGCs) stimulated with recombinant human BMP15 (rhBMP15) and next generation sequencing analysis (NGS) on the identified differentially expressed genes in a selected group of patients with POI were conducted on NGS Illumina platform. In the present study, we obtained 19 differentially expressed genes upon rhBMP15 stimulation in hGCs. Results: showed that all identified genes were upregulated and associated to pluripotency, inhibition of apoptosis, cell proliferation, BMP signaling and apoptosis. Moreover, we identified nine POI patients bearing six rare variants in 5 of the BMP15-induced genes (SAMD11, SMAD6, ID1, USP35, GPCR137C). The BMP15-induced transcriptome analysis in hGCs contributed the understanding of BMP15 role as transcriptional regulator, through the activation of transcriptional repressors, by inducing pathways inhibiting the ovarian follicle maturation, thus possibly maintaining an undifferentiated state of hGCs. These findings lead to the identification of novel candidate genes for POI.

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RNA-Seq Reveals Differentially Expressed Genes and Pathways Affecting Intramuscular Fat Metabolism in Huangshan Black Chicken Population

Journal of Agricultural Science ◽

10.5539/jas.v12n3p117 ◽

2020 ◽

Vol 12 (3) ◽

pp. 117

Author(s):

S. H. Yang ◽

C. S. He ◽

C. H. Li ◽

G. Q. Liu

Keyword(s):

Fatty Acid ◽

Candidate Genes ◽

Meat Quality ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Interaction Network ◽

Intramuscular Fat ◽

Metabolic Process ◽

Differentially Expressed ◽

Thigh Muscle

Intramuscular fat (IMF) plays an important role in meat quality due to its positive correlation with juiciness, tenderness, and flavor. However, for chickens, the molecular mechanisms underlying IMF deposition in thigh muscle have not yet been determined. Here, to identify candidate genes and signaling pathways related to IMF deposition, we deeply explored the chicken transcriptome from thigh muscles of Huangshan Black Chickens with extremely high and low phenotypic values for intramuscular fat content. A total of 128 genes differentially expressed genes (DEGs) were detected, of which 94 were up-regulated and 34 were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed these DEGs (including FABP4, G0S2, PLIN1, SCD1, LFABP, SLC1A6, SLC45A3, ACSBG1, LY86, ST8SIA5, SNAI2, HPGD, EDN2, and THRSP) were significantly enriched in lipid biosynthetic process, steroid biosynthetic and metabolic process, fatty acid metabolic process, and regulation of unsaturated fatty acid metabolic pathways. Additionally, we concluded an interaction network related to lipid metabolism, which might be contributed to the IMF deposition in chicken. Overall, we proposed some new candidate genes and interaction networks that can be associated with IMF deposition and used as biomarkers in meat quality improvement.

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Comparative adipose transcriptome analysis digs out genes related to fat deposition in two pig breeds

Scientific Reports ◽

10.1038/s41598-019-49548-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Kai Xing ◽

Kejun Wang ◽

Hong Ao ◽

Shaokang Chen ◽

Zhen Tan ◽

...

Keyword(s):

Candidate Genes ◽

Signaling Pathway ◽

Meat Quality ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Mapk Signaling ◽

Fat Deposition ◽

Differentially Expressed ◽

Integrated Analysis ◽

Pig Breeds

Abstract Fatness traits are important in pigs because of their implications for fattening efficiency, meat quality, reproductive performance and immunity. Songliao black pigs and Landrace pigs show important differences in production and meat quality traits, including fatness and muscle growth. Therefore, we used a high-throughput massively parallel RNA-seq approach to identify genes differentially expressed in backfat tissue between these two breeds (six pigs in each). An average of 37.87 million reads were obtained from the 12 samples. After statistical analysis of gene expression data by edgeR, a total of 877 differentially expressed genes were detected between the two pig breeds, 205 with higher expression and 672 with lower expression in Songliao pigs. Candidate genes (LCN2, CES3, DGKB, OLR1, LEP, PGM1, PCK1, ACACB, FADS1, FADS2, MOGAT2, SREBF1, PPARGC1B) with known effects on fatness traits were included among the DEGs. A total of 1071 lncRNAs were identified, and 85 of these lncRNAs were differentially expressed, including 53 up-regulated and 32 down-regulated lncRNAs, respectively. The differentially expressed genes and lncRNAs involved in glucagon signaling pathway, glycolysis/gluconeogenesis, insulin signaling pathway, MAPK signaling pathway and so on. Integrated analysis potential trans-regulating or cis-regulating relation between DEGs and DE lncRNAs, suggested lncRNA MSTRG.2479.1 might regulate the expressed level of VLDLR affecting porcine fat metabolism. These results provide a number of candidate genes and lncRNAs potentially involved in porcine fat deposition and provide a basis for future research on the molecular mechanisms underlying in fat deposition.

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