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Codon usage bias (CUB), the uneven usage of synonymous codons encoding the same amino acid, differs among genes within and across bacteria genomes. CUB is known to be influenced by gene expression and accordingly, CUB differs between the high-expression and low-expression genes in several bacteria. In this article, we have extended codon usage study considering gene essentiality as a feature. Using machine learning (ML) based approaches, we have analysed Relative Synonymous Codon Usage (RSCU) values between essential and non-essential genes in Escherichia coli and thirty-four other bacterial genomes whose gene essentiality features were available in public databases. We observed significant differences in codon usage patterns between essential and non-essential genes for majority of the bacterial genomes and accordingly, ML based classifiers achieved high area under curve (AUC) scores, with a minimum score of 70.0 across twenty-eight organisms. Further, importance of the codons towards classifying genes found to differ among the codons in each genome. Arg codon CGT and Gly codon GGT were observed to be the most preferred codons among essential genes in Escherichia coli. Interestingly, some of the codons like CGT, ATA, GGT and GGG observed to be contributing consistently towards classifying essential genes across thirty-five bacteria genomes studied. In other hand, codons TGY and CAY encoding amino acids Cys and His respectively were among the least contributing codons towards classification among all these bacteria. This study demonstrates the gene essentiality based differences in synonymous codon usage in bacteria genomes and presents a common codon usage pattern across bacteria. [ABSTRACT FROM AUTHOR]

The temporary exposure of single-stranded regions in the genome during the process of replication and transcription makes the region vulnerable to cytosine deamination resulting in a higher rate of C→T transition. Intraoperon intergenic regions undergo transcription along with adjacent co-transcribed genes in an operon, whereas interoperon intergenic regions are usually devoid of transcription. Hence these two types of intergenic regions (IGRs) can be compared to find out the contribution of replication-associated mutations (RAM) and transcription-associated mutations (TrAM) towards bringing variation in genomes. In our work, we performed a polymorphism spectra comparison between intraoperon IGRs and interoperon IGRs in genomes of two well-known closely related bacteria such as Escherichia coli and Salmonella enterica. In general, the size of intraoperon IGRs was smaller than that of interoperon IGRs in E. coli and S. enterica. Interestingly, the polymorphism frequency at intraoperon IGRs was 2.5-fold lesser than that in the interoperon IGRs in E. coli genome. Similarly, the polymorphism frequency at intraoperon IGRs was 2.8-fold lesser than that in the inter-operon IGRs in S. enterica genome. Therefore, the intraoperon IGRs were often observed to be more conserved. In the case of interoperon IGRs, the T→C transition frequency was a minimum of two times more frequent than T→A transversion frequency whereas in the case of intraoperon IGRs, T→C transition frequency was similar to that of T→A transversion frequency. The polymorphism was purine-biased and keto-biased more in intraoperon IGRs than the inter-operon IGRs. In E. coli, the transition/transversion ratio was observed as 1.639 and 1.338 in inter-operon and in intraoperon IGRs, respectively. In S. enterica, the transition/transversion ratio was observed as 2.134 and 2.780 in inter-operon and in intraoperon IGRs, respectively. The observation in this study indicates that transcribable IGRs might not always have higher polymorphism frequency than nontranscribable IGRs. The lower polymorphism frequency at intraoperon IGRs might be attributed to different events such as the transcription-coupled DNA repair, sequences facilitating translation initiation and avoidance of Rho-dependent transcription termination. [ABSTRACT FROM AUTHOR]

Transversion and transition mutations have variable effects on the stability of RNA secondary structure considering that the former destabilizes the double helix geometry to a greater extent by introducing purine:purine (R:R) or pyrimidine:pyrimidine (Y:Y) base pairs. Therefore, transversion frequency is likely to be lower than that of transition in the secondary structure regions of RNA genes. Here, we performed an analysis of transition and transversion frequencies in tRNA genes defined well with secondary structure and compared with the intergenic regions in five bacterial species namely Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Staphylococcus aureus and Streptococcus pneumoniae using a large genome sequence data set. In general, the transversion frequency was observed to be lower than that of transition in both tRNA genes and intergenic regions. The transition to transversion ratio was observed to be greater in tRNA genes than that in the intergenic regions in all the five bacteria that we studied. Interestingly, the intraspecies base substitution analysis in tRNA genes revealed that non-compensatory substitutions were more frequent than compensatory substitutions in the stem region. Further, transition to transversion ratio in the loop region was observed to be significantly lesser than that among the non-compensatory substitutions in the stem region. This indicated that the transversion is more deleterious than transition in the stem regions. In addition, substitutions from amino bases (A/C) to keto bases (G/T) were also observed to be more than the reverse substitutions in the stem region. Substitution from amino bases to keto bases are likely to facilitate the stable G:U pairing unlike the reverse substitution that facilitates the unstable A:C pairing in the stem region of tRNA. This work provides additional support that the secondary structure of tRNA molecule is what drives the different substitutions in its gene sequence. [ABSTRACT FROM AUTHOR]

Purpose: To compare the disease characteristics and treatment outcomes of patients with neovascular glaucoma (NVG) presenting with visual acuity (VA) 6/60 or better in two different health systems. Methods: Retrospective chart review of consecutive patients with NVG who presented between January 2016 to January 2018 in 5 tertiary-centres in India and one eye-specialist centre in London (UK) was performed. The baseline characteristics, treatment provisions, and visual outcomes in the India and UK cohorts were compared. Results: At presentation, 18% (83 of 451) and 22% (59 of 270) of patients with NVG had VA 6/60 or better in India and the UK cohorts, respectively. The aetiologies of NVG were similar with proliferative diabetic retinopathy being the most common cause (60.9%, India; 64.4%, UK; p = 0.38). Previous panretinal photocoagulation was more prevalent in the UK cohort compared to the India cohort (94.9% versus 66.3%, respectively; p < 0.001). The mean number of intravitreal anti-VEGF injections per eye was higher in the Indian cohort (1.65 ± 0.97 versus 1.14 ± 1.02 injections; p < 0.001). The number of eyes with closed angles (36.9% India versus 30.5% UK; p = 0.45) and the number of eyes needing glaucoma interventions (52.1% India; 62.7% UK; p = 0.82) were similar in two cohorts. Among glaucoma surgeries, trabeculectomies were more commonly performed in the Indian cohort (23 vs 4; p < 0.001),while glaucoma drainage device surgeries were more prevalent in the UK cohort (18 vs 4 p < 0.001). After a median follow-up of 21 months (IQR 8.4–34.8 India; 24–36 months UK), favourable visual outcomes (vision stable or improved) were similar in both health systems (52.5% in the Indian cohort vs 43.4% in the UK cohort; p = 0.28). On multivariate regression analysis, the need for trans-scleral cyclophotocoagulation was associated with worse visual outcomes in both cohorts. Conclusions: The causes and clinical profile of neovascular glaucoma with presenting visual acuity 6/60 or better in India and the UK were similar. Only up to 50% of eyes achieved favourable visual outcomes with current management protocols in both health systems. [ABSTRACT FROM AUTHOR]