Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

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Understanding the relationship between genotypes and phenotypes is essential to disentangle biological mechanisms and to unravel the molecular basis of diseases. Genes and proteins are closely linked in biological systems. However, genomics and proteomics have developed separately into two distinct disciplines whereby crosstalk among scientists from the two domains is limited and this constrains the integration of both fields into a single data modality of useful information. The emerging field of proteogenomics attempts to address this by building bridges between the two disciplines. In this review, how genomics and transcriptomics data in different formats can be utilized to assist proteogenomics application is briefly discussed. Subsequently, a much larger part of this review focuses on proteogenomics research articles that are published in the last five years that answer two important questions. First, how proteogenomics can be applied to tackle biological problems is discussed, covering genome annotation and precision medicine. Second, the latest developments in analytical technologies for data acquisition and the bioinformatics tools to interpret and visualize proteogenomics data are covered.

Fusobacterium nucleatum is considered to be a key oral bacterium in recruiting periodontal pathogens into subgingival dental plaque. Currently F. nucleatum can be subdivided into five subspecies. Our previous genome analysis of F. nucleatum W1481 (referred to hereafter as W1481), isolated from an 8-mm periodontal pocket in a patient with chronic periodontitis, suggested the possibility of a new subspecies. To further investigate the biology and relationships of this possible subspecies with other known subspecies, we performed comparative analysis between W1481 and 35 genome sequences represented by the five known Fusobacterium subspecies. Our analyses suggest that W1481 is most likely a new F. nucleatum subspecies, supported by evidence from phylogenetic analyses and maximal unique match indices (MUMi). Interestingly, we found a horizontally transferred W1481-specific genomic island harboring the tripartite ATP-independent (TRAP)-like transporter genes, suggesting this bacterium might have a high-affinity transport system for the C4-dicarboxylates malate, succinate, and fumarate. Moreover, we found virulence genes in the W1481 genome that may provide a strong defense mechanism which might enable it to colonize and survive within the host by evading immune surveillance. This comparative study provides better understanding of F. nucleatum and the basis for future functional work on this important pathogen.

Certain classes of antihypertensive drug may exert specific, blood pressure (BP)-independent protective effects on end-organ damages such as left ventricular hypertrophy, although the overall evidence has not been definitive in clinical trials. To unravel antihypertensive drug-induced gene expression changes that are potentially related to the amelioration of end-organ damages, we performed in vivo phenotypic evaluation and transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred strains (ie, hypertensive and normotensive) of rats. We chose 6 antihypertensive classes: enalapril (angiotensin-converting enzyme inhibitor), candesartan (angiotensin receptor blocker), hydrochlorothiazide (diuretics), amlodipine (calcium-channel blocker), carvedilol (vasodilating β-blocker), and hydralazine. In the tested rat strains, 4 of 6 drugs, including 2 renin-angiotensin system inhibitors, were effective for BP lowering, whereas the remaining 2 drugs were not. Besides BP lowering, there appeared to be some interdrug heterogeneity in phenotypic changes, such as suppressed body weight gain and body weight-adjusted heart weight reduction. For the transcriptomic response, a considerable number of genes showed prominent mRNA expression changes either in a BP-dependent or BP-independent manner with substantial diversity between the target organs. Noticeable changes of mRNA expression were induced particularly by renin-angiotensin system blockade, for example, for genes in the natriuretic peptide system ( Nppb and Corin ) in the heart and for those in the renin-angiotensin system/kallikrein-kinin system ( Ren and rat Klk1 paralogs) and those related to calcium ion binding ( Calb1 and Slc8a1 ) in the kidney. The research resources constructed here will help corroborate occasionally inconclusive evidence in clinical settings.