Etiologies underlying subtypes of long-standing type 2 diabetes.

BACKGROUND: Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati ethnic population with long-standing disease, using unsupervised soft clustering, based on etiological determinants. METHODS: The Auto Cluster model in the IBM SPSS Modeler was used to cluster data from 348 Emirati patients with long-standing T2D. Five predictor variables (fasting blood glucose (FBG), fasting serum insulin (FSI), body mass index (BMI), hemoglobin A1c (HbA1c) and age at diagnosis) were used to determine the appropriate number of clusters and their clinical characteristics. Multinomial logistic regression was used to validate clustering results. RESULTS: Five clusters were identified; the first four matched Ahlqvist et al subgroups: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and a fifth new subtype of mild early onset diabetes (MEOD). The Modeler algorithm allows for soft assignments, in which a data point can be assigned to multiple clusters with different probabilities. There were 151 patients (43%) with membership in cluster peaks with no overlap. The remaining 197 patients (57%) showed extensive overlap between clusters at the base of distributions. CONCLUSIONS: Despite the complex picture of long-standing T2D with comorbidities and complications, our study demonstrates the feasibility of identifying subtypes and their underlying causes. While clustering provides valuable insights into the architecture of T2D subtypes, its application to individual patient management would remain limited due to overlapping characteristics. Therefore, integrating simplified, personalized metabolic profiles with clustering holds greater promise for guiding clinical decisions than subtyping alone.

Corrigendum to "Illumina short-read sequencing data, de novo assembly, and annotations of the Drosophila nasuta nasuta genome" [34 (2021) 106674].

[This corrects the article DOI: 10.1016/j.dib.2020.106674.].

De novo assembly, annotation and gene expression profiles of gonads of Cytorace-3, a hybrid lineage of Drosophila nasuta nasuta and D. n. albomicans.

Cytorace-3 is a laboratory evolved hybrid lineage of Drosophila nasuta nasuta males and Drosophila nasuta albomicans females currently passing ~850 generations. To assess interracial hybridization effects on gene expression in Cytorace-3 we profiled the transcriptomes of mature ovaries and testes by employing Illumina sequencing technology and de novo transcriptome assembling strategies. We found 26% of the ovarian, and 14% of testis genes to be differentially expressed in Cytorace-3 relative to the expressed genes in the parental gonadal transcriptomes. About 5% of genes exhibited additive gene expression pattern in the ovary and 3% in the testis, while the remaining genes were misexpressed in Cytorace-3. Nearly 772 of these misexpressed genes in the ovary and 413 in the testis were either over- or under-dominant. Genes following D. n. nasuta dominance was twice (270 genes) than D. n. albomicans dominance (133 genes) in the ovary. In contrast, only 105 genes showed D. n. nasuta dominance and 207 showed D. n. albomicans dominance in testis transcriptome. Of the six expression inheritance patterns, conserved inheritance pattern was predominant for both ovary (73%) and testis (85%) in Cytorace-3. This study is the first to provide an overview of the expression divergence and inheritance patterns of the transcriptomes in an independently evolving distinct hybrid lineage of Drosophila. This recorded expression divergence in Cytorace-3 surpasses that between parental lineages illustrating the strong impact of hybridization driving rapid gene expression changes.

Illumina short-read sequencing data, de novo assembly and annotations of the Drosophila nasuta nasuta genome.

The Drosophila nasuta nasuta (D. n. nasuta) is a member of nasuta subgroup of immigrans species group of Drosophila widely distributed across South-East Asia and central to Southern Africa. It displays morphological similarities with other members of the nasuta subgroup with which it has a recent divergence history. The genomic DNA of D. n. nasuta Coorg strain was paired-end sequenced using Illumina HiSeq 2500 technology to obtain a draft genome assembly of 145.64 Mb. The generated assembly retrieved 93.6% of the conserved dipteran BUSCO orthologs. Approximately 85% of the ab initio predicted proteins exhibit sequence similarity to the proteins of D. albomicans which is the closest annotated species. This draft genome sequence is a valuable resource to Drosophila geneticists and evolutionary biologists to understand molecular organisation of the genome and its evolution during early stages of speciation.

Allopatric sibling species pair Drosophila nasuta nasuta and Drosophila nasuta albomicans exhibit expression divergence in ovarian transcriptomes.

Drosophila nasuta nasuta and Drosophila nasuta albomicans represent cross fertile members of the immigrans species group of Drosophila with an allopatric mode of distribution exhibiting characteristic novelties. Illumina sequencing technology and de novo transcriptome assembling strategies were used for the current study. The analysis revealed 8% of the transcriptome to be differentially expressed between the ovaries of these two species, of which 9% was related to female reproduction. The majority of the differentially expressed genes were enriched for genetic information processing pathways, biosynthesis, and metabolism-related pathways. SNPs in D. n. albomicans transcriptome was double in number than in D. n. nasuta and only 5% of these SNPs were fixed. Ka/Ks ratios indicated the lineages were under strong purifying selection. The genes which are differentially expressed are evolving at a similar rate as that of genes with conserved expression. Thus, the current findings provide useful insights on the expression dynamics during incipient species divergence of D. n. nasuta and D. n. albomicans since their divergence time of ~ 0.5 million years.