Reconstructing the phylodynamic history and geographic spread of the CRF01_AE-predominant HIV-1 epidemic in the Philippines from PR/RT sequences sampled from 2008 to 2018.

The Philippines has had a rapidly growing human immunodeficiency virus (HIV) epidemic with a shift in the prevalent subtype from B to CRF01_AE. However, the phylodynamic history of CRF01_AE in the Philippines has yet to be reconstructed. We conducted a descriptive retrospective study reconstructing the history of HIV-1 CRF01_AE transmissions in the Philippines through molecular epidemiology. Partial polymerase sequences (n = 1144) collected between 2008 and 2018 from three island groups were collated from the Research Institute for Tropical Medicine drug resistance genotyping database. Estimation of the time to the most recent common ancestor (tMRCA), effective reproductive number (Re), effective viral population size (Ne), relative migration rates, and geographic spread of CRF01_AE was performed with BEAST. Re and Ne were compared between CRF01_AE and B. Most CRF01_AE sequences formed a single clade with a tMRCA of June 1996 [95 per cent highest posterior density (HPD): December 1991, October 1999]. An increasing CRF01_AE Ne was observed from the tMRCA to 2013. The CRF01_AE Re reached peaks of 2.46 [95 per cent HPD: 1.76, 3.27] in 2007 and 2.52 [95 per cent HPD: 1.83, 3.34] in 2015. A decrease of CRF01_AE Re occurred in the intervening years of 2007 to 2011, reaching as low as 1.43 [95 per cent HPD: 1.06, 1.90] in 2011, followed by a rebound. The CRF01_AE epidemic most likely started in Luzon and then spread to the other island groups of the country. Both CRF01_AE and Subtype B exhibited similar patterns of Re fluctuation over time. These results characterize the subtype-specific phylodynamic history of the largest CRF01_AE cluster in the Philippines, which contextualizes and may inform past, present, and future public health measures toward controlling the HIV epidemic in the Philippines.

Differential gene expression and network-based analyses of the placental transcriptome reveal distinct potential biomarkers for gestationaldiabetes mellitus.

AIMS: Gestational diabetes mellitus (GDM) is a common complication during pregnancy affecting the mother and fetus. With the problems encountered with the oral glucose tolerance test (OGTT), we aim to identify potential early biomarkers of GDM. METHODS: A cross-sectional study was conducted among 80 pregnant women. Blood samples were collected every trimester, and total RNA was isolated. After quality control and library preparation, next-generation sequencing was performed. Differential expression analysis was done. Enriched Gene Ontology: Biological Processes (GO: BP) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified. Gene co-expression networks were constructed. Protein-protein Interaction (PPI) networks were then built from modules significantly correlated with Hemoglobin A1c. Genes with the highest degree of interaction were identified as hub genes. RESULTS: IGKV2D-28 and PTPRG were consistently differentially expressed among the three comparisons. Top enriched GO: BP terms and KEGG pathways are linked to immune responses. Orange (r = 0.59, p = 0.02) and purple modules (r = 0.41, p = 0.02) of the GDM cohorts in the first and second trimesters, respectively, significantly correlated with Hemoglobin A1c. HDAC8 of the orange module and MPO and CRISP3 of the purple module were identified as hub genes. CONCLUSIONS: In this study, potential biomarkers of GDM were identified, namely, IGKV2D-28, PTPRG, HDAC8, MPO, and CRISP3.