Genes

Background/Objectives: Integrating transcriptomic evidence across organs is limited by heterogeneity between cohorts, so reproducible cross-organ signals are usually reported as gene lists rather than as validated candidates. We therefore developed and applied a cross-organ integration framework in which discovery is separated from adjudication. Methods: Eight public bulk transcriptomic cohorts (six hepatic, two gastric) were combined by robust rank aggregation, and the shared candidates were carried into a pre-specified robustness audit combining leave-one-dataset-out recalculation, effect-size meta-analysis, and cell-composition correction. The candidate set was not re-selected after discovery, and the retained candidates were tested in two independent, non-discovery external cohorts. Results: Applied to metabolic dysfunction-associated steatotic liver disease and chronic atrophic gastritis, the framework returned four genes: CDHR2 and ANXA4 defined an epithelial pattern, IL32 an immune-associated pattern at the epithelial interface, and CADM2 a hepatic stellate-cell pattern; LGALS3 was retained separately as a composition-sensitive control. Every retained candidate kept its discovery-stage direction in both held-out cohorts. In the gastric replication cohort, where the test is run across ten pooled libraries, CDHR2 and CADM2 remained significant after Benjamini–Hochberg correction (both q = 0.020); for the other three candidates, the gastric contrast was directional only. In single-cell and single-nucleus data, the candidates resolved into three cell-state patterns that matched independent protein-level annotations, and exploratory Mendelian randomization returned no concordant, FDR-supported genetic evidence. Conclusions: Three of the five candidates (CDHR2, CADM2 and IL32) met all three prespecified criteria for the higher evidence tier and two (ANXA4 and LGALS3) the lower one. What the data establish is cross-disease transcriptional concordance along the gut–liver axis, interpreted through shared cell-state localization, rather than a shared etiology, a causal relationship, or a common biomarker. The audit framework is directly transferable to other cross-organ comparisons, and the five genes are reported as expression-supported candidates ready for experimental follow-up.

Background/Objectives: Citrobacter farmeri and Enterobacter cloacae are opportunistic Enterobacteriaceae recovered from unhatched Chelonia mydas eggs, but their secondary metabolite and metabolic potential remain unresolved. This study examines which predicted differences between one isolate of each taxon are specific to the isolates and which are shared with public genomes of the same species. Methods: antiSMASH v7.1.0, KofamScan/KEGG-Decoder module profiling (178 modules) with BLASTP verification, and curated CarveMe v1.6.6 genome-scale metabolic modeling were applied to the draft genomes of both isolates. In addition, 18 public genomes (nine C. farmeri; nine labelled E. cloacae, six of them the isolate’s species by average nucleotide identity) were screened with tblastn and uniformly built models. Results: Both isolates carried an enterobactin cluster; E. cloacae also carried an aerobactin cluster and C. farmeri a lower-confidence homoserine lactone synthase. Fourteen of 178 modules differed, notably a cytochrome bc1 complex with c-type cytochromes in C. farmeri versus a Na⁺-translocating NADH:quinone oxidoreductase (Na⁺-NQR) operon in E. cloacae. Modeled biosynthetic capacities differed by at most 9.1%. Every presence/absence difference was reproduced in the public genomes (bc1 in 9/9 C. farmeri and 0/9 E. cloacae-labelled genomes; Na⁺-NQR, pga and iucABCD in 9/9 E. cloacae-labelled and 0/9 C. farmeri genomes); only the Type II secretion cluster varied (absent in 1/9 E. cloacae-labelled genomes). Modeled differences between the isolates matched those among genomes of the same species. Conclusions: The differences are lineage-level features, not isolate-specific traits, and the data do not link them to the turtle-egg niche; all findings are computational predictions requiring phenotypic confirmation.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disorder characterized by fibrous or fibro-fatty myocardial tissue replacement leading to the life-threatening ventricular arrhythmias and progressive heart failure (HF). Most of the known genetic subtypes of ARVC, including the DSG2-associated form, are characterized by an autosomal dominant pattern of inheritance. Cases of compound heterozygous and digenic forms of ARVC are relatively rare and typically manifest in childhood or adolescence. The aim of this study is to characterize a rare biallelic form of ARVC caused by a homozygous mutation c.581C>T (p.Ser194Leu) in the DSG2 gene based on our own and published data. Methods: The study cohort included 80 probands who underwent clinical examination and genetic testing using NGS of 16 genes. Haplotype analysis was performed for the probands homozygous for the DSG2 c.581C>T (p.Ser194Leu) variant. Results: The rare form of ARVC was identified in three probands originating from the Republic of Dagestan and representing Dargin ethnic group. We assessed the frequency of the minor T allele in groups of 150 healthy volunteers, including 20 from the Republic of Dagestan, and 300 cardiomyopathy patients who are presumably natives of the North Caucasian Highland Region. The c.581C>T (p.Ser194Leu) variant was not detected in any of the DNA samples analyzed, indicating the rarity of this form of ARVC. The fact that three probands with the rare form of ARVC originate from the same minor ethnicity (Dargins) with a high rate of consanguineous marriages suggests a common ancestor for these families. All three probands shared a haplotype of approximately 4.01 Mb surrounding DSG2 c.581C>T. Conclusions: Our study contributes to expanding the knowledge of the molecular causes of cardiomyopathies in poorly studied populations, underrepresented in international databases, and to establishing genotype–phenotypic correlations.