Abstract
α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia ...carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/−−
SEA
(4.066%), αα/−α
3.7
(2.934%), αα/−α
4.2
(0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14–99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (−α
3.7
/−α
4.2
, αα/−−
THAI
, −α
3.7
/−−
SEA
, −α
4.2
/−−
SEA
). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/−−
SEA
, 94.87% for αα/−α
3.7
, and 96.51% for αα/−α
4.2
; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT.
Abstract Background Cell free DNA (cfDNA)-based assays hold great potential in detecting early cancer signals yet determining the tissue-of-origin (TOO) for cancer signals remains a challenging task. ...Here, we investigated the contribution of a methylation atlas to TOO detection in low depth cfDNA samples. Methods We constructed a tumor-specific methylation atlas (TSMA) using whole-genome bisulfite sequencing (WGBS) data from five types of tumor tissues (breast, colorectal, gastric, liver and lung cancer) and paired white blood cells (WBC). TSMA was used with a non-negative least square matrix factorization (NNLS) deconvolution algorithm to identify the abundance of tumor tissue types in a WGBS sample. We showed that TSMA worked well with tumor tissue but struggled with cfDNA samples due to the overwhelming amount of WBC-derived DNA. To construct a model for TOO, we adopted the multi-modal strategy and used as inputs the combination of deconvolution scores from TSMA with other features of cfDNA. Results Our final model comprised of a graph convolutional neural network using deconvolution scores and genome-wide methylation density features, which achieved an accuracy of 69% in a held-out validation dataset of 239 low-depth cfDNA samples. Conclusions In conclusion, we have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.
Breast cancer is the leading cause of cancer death in Vietnamese women, but its mutational landscape and actionable alterations for targeted therapies remain unknown. After treatment, a sensitive ...biomarker to complement conventional imaging to monitor patients is also lacking. In this prospective multi‐center study, 134 early‐stage breast cancer patients eligible for curative‐intent surgery were recruited. Genomic DNA from tumor tissues and paired white blood cells were sequenced to profile all tumor‐derived mutations in 95 cancer‐associated genes. Our bioinformatic algorithm was then utilized to identify top mutations for individual patients. Serial plasma samples were collected before surgery and at scheduled visits after surgery. Personalized assay tracking the selected mutations were performed to detect circulating tumor DNA (ctDNA) in the plasma. We found that the mutational landscape of the Vietnamese was largely similar to other Asian cohorts, showing higher TP53 mutation frequency than in Caucasians. Alterations in PIK3CA and PI3K signaling were dominant, particularly in our triple‐negative subgroup. Using top‐ranked mutations, we detected ctDNA in pre‐operative plasma in 24.6–43.5% of the hormone‐receptor‐positive groups and 76.9–80.8% of the hormone‐receptor‐negative groups. The detection rate was associated with breast cancer subtypes and clinicopathological features that increased the risk of relapse. Interim analysis after a 15‐month follow‐up revealed post‐operative detection of ctDNA in all three patients that had recurrence, with a lead time of 7–13 months ahead of clinical diagnosis. Our personalized assay is streamlined and affordable with promising clinical utility in residual cancer surveillance. We also generated the first somatic variant dataset for Vietnamese breast cancer women that could lay the foundation for precision cancer medicine in Vietnam.
The authors determine, for the first time, the somatic variant landscape of Vietnamese women with breast cancer, and establish a personalized tumor‐informed assay (K‐Track®) to detect ctDNA in liquid biopsy. This assay is streamlined and affordable, with promising clinical utilities in both residual cancer surveillance and actionable mutation profiling for breast cancer patients.
Purpose of the study: Alzheimer's disease (AD) is the most common type of dementia and its prevalence is rapidly increasing worldwide. Early-onset Alzheimer's disease (EOAD) constitutes of patients ...with age of onset earlier than 65 year-old and is known to be associated with genetic mutations. In this study, we reported the first genetic analysis of Vietnamese patients with EOAD.
Materials and methods: We analyzed targeted sequencing data obtained from a cohort of 51 Vietnamese EOAD patients to identify pathogenic variants in twenty nine well-characterized neurodengerative genes.
Results: We identified four missense mutations in APP/PSEN1 genes from six individuals, which accounts for 11.8% of all tested cases. Three of these mutations were previously reported as pathogenic and one mutation in the APP gene was newly identified and might be specific for Vietnamese patients. Our study also found eight individuals carrying homozygous APOE ε4 allele, the main risk factor gene for late-onset AD.
Conclusions: Our findings showed that mutation rate in APP/PSEN genes in Vietnamese EOAD patients is consistent with that in other ethnic groups. Although further functional studies are required to validate the pathogenesis of the new mutations, our study demonstrated the necessity of genetic screening for EOAD patients as well as additional genetic data collection in Vietnamese population.
This article proposes a distributed consensus-based control algorithm based on the voltage shifting method for the secondary control layer of the hierarchical control structure in DC microgrids to ...attain both precise proportional power sharing and DC bus voltage restoration when the microgrid is isolated from the utility grid. The proposed algorithm implemented two unity gain integrators for each distributed controller, one is for ensuring proportional power sharing and the other is for restoring local DC bus voltage, and a low-bandwidth communication network to transfer information between converters. For the proposed strategy, each converter only needs to broadcast its p.u value, which is characterized by the relation between the current output power and the converter rated output power, and receive the voltage measurement from the nearest measure station on the DC bus. Voltage shifting terms will be calculated locally by distributed controllers, reducing the risk of having a single point of failure in the system as opposed to a centralized algorithm. When all converter p.u values converged to a universal value, proportional power sharing will be attained. The stability and effectiveness of the proposed algorithm will be evaluated using PLECS simulations and tested with an experimental DC microgrid setup.
Các hoạt động gấp giấy với số lượng lớn như giấy báo thi, giấy báo trúng tuyển, giấy báo thuế,… mất nhiều thời gian và nhàm chán. Do đó, nếu có máy gấp giấy hỗ trợ công tác này sẽ mang lại rất nhiều ...lợi ích cho cả nhân công và cơ quan quản lý. Trong nghiên cứu này, một giải pháp thiết kế máy gấp giấy tự động được đề xuất để hỗ trợ các công tác nêu trên. Máy bao gồm hai bộ phận chính: cơ cấu cơ khí để kéo và gấp giấy, mạch điều khiển để điều khiển tất cả các hoạt động của máy. Hơn nữa, máy có thể đếm và hiển thị số tờ đã được gấp trên màn hình tinh thể lỏng LCD (Liquid Crystal Display). Máy có thể gấp khổ giấy A4 (21 cm × 29.7 cm) thành ba phần đều nhau. Giấy sau khi in được gấp làm ba và có thể đặt trong bì thư với tên và địa chỉ người nhận được đặt ở vị trí màng nhựa trong suốt. Giải pháp này có thể giúp giảm thiểu công việc văn thư nhàm chán (in tên, địa chỉ và gấp giấy) và tăng năng suất lao động. Kết quả chạy thử nghiệm cho thấy, máy hoạt động ổn định và đạt năng suất 960 tờ/giờ. Với kết quả đạt được, nhóm tác giả mạnh dạn đề xuất áp dụng máy này vào công tác văn thư tại các trường học, các cơ quan thuế hay bảo hiểm xã hội ở Việt Nam.
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