KaMRaT: a C++ toolkit for k-mer count matrix dimension reduction.

MOTIVATION: KaMRaT is designed for processing large k-mer count tables derived from multi-sample, RNA-seq data. Its primary objective is to identify condition-specific or differentially expressed sequences, regardless of gene or transcript annotation. RESULTS: KaMRaT is implemented in C++. Major functions include scoring k-mers based on count statistics, merging overlapping k-mers into contigs and selecting k-mers based on their occurrence across specific samples. AVAILABILITY AND IMPLEMENTATION: Source code and documentation are available via https://github.com/Transipedia/KaMRaT.

Estimation of the incubation period of COVID-19 in Vietnam.

OBJECTIVE: To estimate the incubation period of Vietnamese confirmed COVID-19 cases. METHODS: Only confirmed COVID-19 cases who are Vietnamese and locally infected with available data on date of symptom onset and clearly defined window of possible SARS-CoV-2 exposure were included. We used three parametric forms with Hamiltonian Monte Carlo method for Bayesian Inference to estimate incubation period for Vietnamese COVID-19 cases. Leave-one-out Information Criterion was used to assess the performance of three models. RESULTS: A total of 19 cases identified from 23 Jan 2020 to 13 April 2020 was included in our analysis. Average incubation periods estimated using different distribution model ranged from 6.0 days to 6.4 days with the Weibull distribution demonstrated the best fit to the data. The estimated mean of incubation period using Weibull distribution model was 6.4 days (95% credible interval (CrI): 4.89-8.5), standard deviation (SD) was 3.05 (95%CrI 3.05-5.30), median was 5.6, ranges from 1.35 to 13.04 days (2.5th to 97.5th percentiles). Extreme estimation of incubation periods is within 14 days from possible infection. CONCLUSION: This analysis provides evidence for an average incubation period for COVID-19 of approximately 6.4 days. Our findings support existing guidelines for 14 days of quarantine of persons potentially exposed to SARS-CoV-2. Although for extreme cases, the quarantine period should be extended up to three weeks.

Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro.

Our understanding of human germ cell development is limited in large part due to inaccessibility of early human development to molecular genetic analysis. Pluripotent human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been shown to differentiate to cells of all three embryonic germ layers, as well as germ cells in vitro, and thus may provide a model for the study of the genetics and epigenetics of human germline. Here, we examined whether intrinsic germ cell translational, rather than transcriptional, factors might drive germline formation and/or differentiation from human pluripotent stem cells in vitro. We observed that, with overexpression of VASA (DDX4) and/or DAZL (Deleted in Azoospermia Like), both hESCs and iPSCs differentiated to primordial germ cells, and maturation and progression through meiosis was enhanced. These results demonstrate that evolutionarily unrelated and divergent RNA-binding proteins can promote meiotic progression of human-derived germ cells in vitro. These studies describe an in vitro model for exploring specifics of human meiosis, a process that is remarkably susceptible to errors that lead to different infertility-related diseases.

Endothelial cells derived from human iPSCS increase capillary density and improve perfusion in a mouse model of peripheral arterial disease.

OBJECTIVE: Stem cell therapy for angiogenesis and vascular regeneration has been investigated using adult or embryonic stem cells. In the present study, we investigated the potential of endothelial cells (ECs) derived from human induced pluripotent stem cells (hiPSCs) to promote the perfusion of ischemic tissue in a murine model of peripheral arterial disease. METHODS AND RESULTS: Endothelial differentiation was initiated by culturing hiPSCs for 14 days in differentiation media supplemented with BMP-4 and vascular endothelial growth factor. The hiPSC-ECs exhibited endothelial characteristics by forming capillary-like structures in matrigel and incorporating acetylated-LDL. They stained positively for EC markers such as KDR, CD31, CD144, and eNOS. In vitro exposure of hiPSC-ECs to hypoxia resulted in increased expression of various angiogenic related cytokines and growth factors. hiPSC-ECs were stably transduced with a double fusion construct encoded by the ubiquitin promoter, firefly luciferase for bioluminescence imaging and green fluorescence protein for fluorescent detection. The hiPSC-ECs (5×10(5)) were delivered by intramuscular injection into the ischemic hindlimb of SCID mice at day 0 and again on day 7 after femoral artery ligation (n=8). Bioluminescence imaging showed that hiPSC-ECs survived in the ischemic limb for at least 2 weeks. In addition, laser Doppler imaging showed that the ratio of blood perfusion was increased by hiPSC-EC treatment by comparison to the saline-treated group (0.58±0.12 versus 0.44±0.04; P=0.005). The total number of capillaries in the ischemic limb of mice receiving hiPSC-EC injections was greater than those in the saline-treated group (1284±155 versus 797±206 capillaries/mm(2)) (P<0.002). CONCLUSION: This study is a first step toward development of a regenerative strategy for peripheral arterial disease based on the use of ECs derived from hiPSCs.