Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights into Cardiovascular Disease

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1,301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan ® ). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥ 5. Results were validated using an alternative, antibody-based, proteomic platform (Olink ® ) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study. Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8 × 10 −11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β = 0.61±0.05, p-value = 3.27 × 10 −30 ) and MMP-3 (β = -0.60±0.05, p = 1.67 × 10 −32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with nine proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1 associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β = 0.34±0.04, p = 1.34 × 10 −17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation and myocardial function.

High-quality whole-genome sequence analysis of Lactobacillus paragasseri UBLG-36 reveals oxalate-degrading potential of the strain

Lactobacillus paragasseri was identified as a novel sister taxon of L. gasseri in 2018. Since the reclassification of L. paragasseri, there has been hardly any report describing the probiotic properties of this species. In this study, an L. paragasseri strain UBLG-36 was sequenced and analyzed to determine the molecular basis that may confer the bacteria with probiotic potential. UBLG-36 was previously documented as an L. gasseri strain. Average nucleotide identity and phylogenomic analysis allowed accurate taxonomic identification of UBLG-36 as an L. paragasseri strain. Analysis of the draft genome (~1.94 Mb) showed that UBLG-36 contains 5 contigs with an average G+C content of 34.85%. Genes essential for the biosynthesis of bacteriocins, adhesion to host epithelium, stress resistance, host immunomodulation, defense, and carbohydrate metabolism were identified in the genome. Interestingly, L. paragasseri UBLG-36 also harbored genes that code for enzymes involved in oxalate catabolism, such as formyl coenzyme A transferase (frc) and oxalyl coenzyme A decarboxylase (oxc). In vitro oxalate degradation assay showed that UBLG-36 is highly effective in degrading oxalate (averaging more than 45% degradation), a feature that has not been reported before. As a recently identified bacterium, there are limited genomic reports on L. paragasseri, and our draft genome sequence analysis is the first to describe and emphasize the probiotic potential and oxalate degrading ability of this species. With results supporting the probiotic functionalities and oxalate catabolism of UBLG-36, we propose that this strain is likely to have immense biotechnological applications upon appropriate characterization.

The epidemiology of AmpC-producing Escherichia coli isolated from dairy cattle faeces on pasture-fed farms

Introduction. Antibiotic use, particularly amoxicillin-clavulanic acid in dairy farming, has been associated with an increased incidence of AmpC-hyperproducing Escherichia coli . Gap statement. There is limited information on the incidence of AmpC-hyperproducing E. coli from seasonal pasture-fed dairy farms. Aim. We undertook a New Zealand wide cross-sectional study to determine the prevalence of AmpC-producing E. coli carried by dairy cattle. Methodology. Paddock faeces were sampled from twenty-six dairy farms and were processed for the selective growth of both extended-spectrum beta-lactamase (ESBL)- and AmpC-producing E. coli . Whole genome sequence analysis was carried out on 35 AmpC-producing E. coli . Results. No ESBL- or plasmid mediated AmpC-producing E. coli were detected, but seven farms were positive for chromosomal mediated AmpC-hyperproducing E. coli . These seven farms were associated with a higher usage of injectable amoxicillin antibiotics. Whole genome sequence analysis of the AmpC-producing E. coli demonstrated that the same strain (<3 SNPs difference) of E. coli ST5729 was shared between cows on a single farm. Similarly, the same strain (≤15 SNPs difference) of E. coli ST8977 was shared across two farms (separated by approximately 425 km). Conclusion. These results infer that both cow-to-cow and farm-to-farm transmission of AmpC-producing E. coli has occurred.

Bioinformatics Analysis Identifies a Small ORF in the Genome of Fish Nidoviruses of Genus Oncotshavirus Predicted to Encode a Novel Integral Protein

Genome sequence analysis of Atlantic salmon bafinivirus (ASBV) revealed a small open reading frame (ORF) predicted to encode a Type I membrane protein with an N-terminal cleaved signal sequence (110 aa), likely an envelope (E) protein. Bioinformatic analyses showed that the predicted protein is strikingly similar to the coronavirus E protein in structure. This is the first report to identify a putative E protein ORF in the genome of members of the Oncotshavirus genus (subfamily Piscavirinae, family Tobaniviridae, order Nidovirales) and, if expressed would be the third family (after Coronaviridae and Arteriviridae) within the order to have the E protein as a major structural protein.

Prevalence and Molecular Characterization of Novel Pathogenic Strains of Macrococcus Caseolyticus Isolated From External Wounds of Donkeys in Khartoum State –Sudan

A pathogenic strains of Macrococcus caseolyticus was isolated from wounds infection during investigation on donkeys in Khartoum State. Samples were collected from external wounds (head, abdomin, back and leg), during different seasons of the year. One isolate (124B) was identified using whole-genome sequence analysis. RAST software identified thirty-one virulent genes of disease and defense including methicillin resistant genes, TatR family and ANT(4’)-Ib. Plasmid rep22 wasidentified by PlasmidFindet-2.0 Server and a CRISPR. MILST-2.0 predicted many novel alleles. NCBI notated the genome as a novel strain of M.caseolyticus strain (DaniaSudan). The MLST-tree-V1 revealed that DaniaSudan and KM0211a strains were interrelated. Strain Daniasudan was resistant to ciprofloxacin, ceftazidime, erythromycin, oxacillin, clindamycin and kanamycin. The prevalence of the strain was 4.73%, with significant differences between collection seasons and locations of wounds. Mice modling showen bacteremia and many clinical (swelling, allergy, wounds and loss of hair). Enlarged, hyperemia, adhesions and abscesses were observed in many organs. This represents the first report of pathogenic strains of M.caseolyticus worldwide.