David S. Tsao, Sukrit Silas, Brian P. Landry, Nelda P. Itzep, Amy B. Nguyen, Samuel Greenberg, Celeste K. Kanne, Vivien A. Sheehan, Rani Sharma, Rahul Shukla, Prem N. Arora, Oguzhan Atay <<<

Abstract Next-generation DNA sequencing is currently limited by an inability to accurately count the number of input DNA molecules. Molecular counting is particularly needed when accurate quantification is required for diagnostic purposes, such as in single gene non-invasive prenatal testing (sgNIPT) and liquid biopsy. We developed Quantitative Counting Template (QCT) molecular counting to reconstruct the number of input DNA molecules using sequencing data. We then used QCT molecular counting to develop sgNIPTs of sickle cell disease, cystic fibrosis, spinal muscular atrophy, alpha-thalassemia, and beta-thalassemia. The analytical sensitivity and specificity of sgNIPT was >98% and >99%, respectively. Validation of sgNIPTs was further performed with maternal blood samples collected during pregnancy, and sgNIPTs were 100% concordant with newborn follow-up. <<<

Jiale Xiang, Xiangzhong Sun, Jiguang Peng, Hongfu Zhang, Jiankun Shen, Jingrou Li, Hongyu Li, Lanping Hu, Jingjing Zhang, Shihao Zhou, Sihu Xu, Yun Yang, Jun He, Zhiyu Peng <<<

L. F. Johansson, E. N. de Boer, H. A. de Weerd, F. van Dijk, M. G. Elferink, G. H. Schuring-Blom, R. F. Suijkerbuijk, R. J. Sinke, G. J. te Meerman, R. H. Sijmons, M. A. Swertz, B. Sikkema-Raddatz <<<

AbstractNon-invasive prenatal testing (NIPT) of cell-free DNA in maternal plasma, which is a mixture of maternal DNA and a low percentage of fetal DNA, can detect fetal aneuploidies using massively parallel sequencing. Because of the low percentage of fetal DNA, methods with high sensitivity and precision are required. However, sequencing variation lowers sensitivity and hampers detection of trisomy samples. Therefore, we have developed three algorithms to improve sensitivity and specificity: the chi-squared-based variation reduction (χ2VR), the regression-based Z-score (RBZ) and the Match QC score. The χ2VR reduces variability in sequence read counts per chromosome between samples, the RBZ allows for more precise trisomy prediction, and the Match QC score shows if the control group used is representative for a specific sample. We compared the performance of χ2VR to that of existing variation reduction algorithms (peak and GC correction) and that of RBZ to trisomy prediction algorithms (standard Z-score, normalized chromosome value and median-absolute-deviation-based Z-score). χ2VR and the RBZ both reduce variability more than existing methods, and thereby increase the sensitivity of the NIPT analysis. We found the optimal combination of algorithms was to use both GC correction and χ2VR for pre-processing and to use RBZ as the trisomy prediction method. <<<

AbstractWith the further transformation of The Large Sky Area Multi-Object Fiber Spectroscopic Telescope, the new generation of fiber positioner robot chooses a 4 mm hollow cup motor with minimum phase inductance. Because the load of the fiber positioner robot is constant and the inertia of the motor is very small, an open loop positioning control method based on Space Vector Pulse Width Modulation is proposed, and the specific open loop parameters are directly tuned by relevant experimental strategies. The critical factors of the open loop driving mode are discussed in detail from four aspects: subdivision, fundamental frequency, wave generation mode and peak current. Based on the actual fiber positioner robot, the hardware driver and assessment platform are built. The positioning tests show that the method proposed is practical and effective, and meets the precision positioning demand of the new generation optical fiber positioner robot. <<<