Bridging the TB data gap: in silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data

YesBackground: Mycobacterium tuberculosis rapid diagnostic tests (RDTs) are widely employed in routine laboratories and national surveys for detection of rifampicinresistant (RR)-TB. However, as next-generation sequencing technologies have become more commonplace in research and surveillance programs, RDTs are being increasingly complemented by whole genome sequencing (WGS). While comparison between RDTs is difficult, all RDT results can be derived from WGS data. This can facilitate continuous analysis of RR-TB burden regardless of the data generation technology employed. By converting WGS to RDT results, we enable comparison of data with different formats and sources particularly for low- and middle-income high TB-burden countries that employ different diagnostic algorithms for drug resistance surveys. This allows national TB control programs (NTPs) and epidemiologists to utilize all available data in the setting for improved RR-TB surveillance. Methods: We developed the Python-based MycTB Genome to Test (MTBGT) tool that transforms WGS-derived data into laboratory-validated results of the primary RDTs—Xpert MTB/RIF, XpertMTB/RIF Ultra, GenoType MDRTBplus v2.0, and GenoscholarNTM+MDRTB II. The tool was validated through RDT results of RR-TB strains with diverse resistance patterns and geographic origins and applied on routine-derived WGS data. Results: The MTBGT tool correctly transformed the single nucleotide polymorphism (SNP) data into the RDT results and generated tabulated frequencies of the RDT probes as well as rifampicin-susceptible cases. The tool supplemented the RDT probe reactions output with the RR-conferring mutation based on identified SNPs. The MTBGT tool facilitated continuous analysis of RR-TB and Xpert probe reactions from different platforms and collection periods in Rwanda. Conclusion: Overall, the MTBGT tool allows low- and middle-income countries to make sense of the increasingly generated WGS in light of the readily available RDT.Erasmus Mundus Joint Doctorate Fellowship grant 2016- 1346

Association analysis of-429T/C and-374T/A polymorphisms of receptor of advanced glycation end products (RAGE) gene in Malaysian with type 2 diabetic retinopathy

Conflicting results have been reported in different populations on the association between two particular RAGE gene polymorphisms (-429T/C and -374T/A) and retinopathy in diabetic patients. Therefore this study was designed to assess the association between both gene polymorphisms with retinopathy in Malaysian diabetic patients. A total of 342 type 2 diabetic patients 171 without retinopathy (DNR) and 171 with retinopathy (DR) and 235 healthy controls were included in this study. Genomic DNA was obtained from blood samples and the screening for the gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism approach. Overall, the genotype distribution for both polymorphisms was not statistically different (p > 0.05) among the control, DNR and DR groups. The -429C minor allele frequency of DR group (12.0%) was not significantly different (p > 0.05) when compared to DNR group (16.1%) and healthy controls (11.3%). The -374A allele frequency also did not differ significantly between the control and DNR (p > 0.05), control and DR (p > 0.05) as well as DNR and DR groups (p > 0.05). This is the first study report on RAGE gene polymorphism in Malaysian DR patients. In conclusion, -429T/C and -374T/A polymorphisms in the promoter region of RAGE gene were not associated with Malaysian type 2 DR patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy

Purpose In this study, we aimed to investigate the possible association between SLC2A126177A/Gpolymorphism and diabetic retinopathy (DR) in Malaysianpatients with type 2 diabetes. Methods Genomic DNA was extracted from 211 Malaysian type 2 diabeticpatients (100 without retinopathy DNR, 111 with retinopathy) and 165 healthy controls. A highresolutionmelting assay developed in this study was used to detect SLC2A126177A/Gpolymorphism followed by statistical analysis. Results A statistically significant difference in 26177 G minor allele frequency between healthy controls (19.7 %) and total patient group (26.1 %) (p 0.05). Conclusions This is the first study which shows that SLC2A1 26177G allele is associated with type 2 diabetes in Malaysian population but not with DR