| 1. |
- Xiao, Wenming, et al.
(författare)
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Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1141-1150
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Tidskriftsartikel (refereegranskat)abstract
- Recommendations are given on optimal read coverage and selection of calling algorithm to maximize the reproducibility of cancer mutation detection in whole-genome or whole-exome sequencing. Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.
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| 2. |
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| 3. |
- Zhao, Yongmei, et al.
(författare)
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Whole genome and exome sequencing reference datasets from a multi-center and cross-platform benchmark study
- 2021
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- With the rapid advancement of sequencing technologies, next generation sequencing (NGS) analysis has been widely applied in cancer genomics research. More recently, NGS has been adopted in clinical oncology to advance personalized medicine. Clinical applications of precision oncology require accurate tests that can distinguish tumor-specific mutations from artifacts introduced during NGS processes or data analysis. Therefore, there is an urgent need to develop best practices in cancer mutation detection using NGS and the need for standard reference data sets for systematically measuring accuracy and reproducibility across platforms and methods. Within the SEQC2 consortium context, we established paired tumor-normal reference samples and generated whole-genome (WGS) and whole-exome sequencing (WES) data using sixteen library protocols, seven sequencing platforms at six different centers. We systematically interrogated somatic mutations in the reference samples to identify factors affecting detection reproducibility and accuracy in cancer genomes. These large cross-platform/site WGS and WES datasets using well-characterized reference samples will represent a powerful resource for benchmarking NGS technologies, bioinformatics pipelines, and for the cancer genomics studies.
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| 4. |
- Fang, Li Tai, et al.
(författare)
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Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1151-1160
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-normal paired DNA samples from a breast cancer cell line and a matched lymphoblastoid cell line enable calibration of clinical sequencing pipelines and benchmarking 'tumor-only' or 'matched tumor-normal' analyses. The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.
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| 5. |
- Chen, Jie, et al.
(författare)
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Risk of incident cardiovascular disease among patients with gastrointestinal disorder : a prospective cohort study of 330,751 individuals.
- 2023
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - 2058-5225 .- 2058-1742.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The associations between gastrointestinal diseases (GIs) and cardiovascular disease (CVD) were unclear. We conducted a prospective cohort study to explore their associations.METHODS: This study included 330 751 individuals without baseline CVD from the UK Biobank cohort. Individuals with and without GIs were followed up until the ascertainment of incident CVDs, including coronary heart disease (CHD), cerebrovascular disease (CeVD), heart failure (HF) and peripheral artery disease (PAD). The diagnosis of diseases was confirmed with combination of the nationwide inpatient data, primary care data, and cancer registries. A multivariable Cox proportional hazard regression model was used to estimate the associations between GIs and the risk of incident CVD.RESULTS: During a median follow-up of 11.8 years, 31 605 incident CVD cases were diagnosed. Individuals with GIs had an elevated risk of CVD (hazard ratio 1.37; 95% confidence interval 1.34-1.41, P < 0.001). Eleven out of fifteen GIs were associated with an increased risk of CVD after Bonferroni-correction, including cirrhosis, non-alcoholic fatty liver disease, gastritis and duodenitis, irritable bowel syndrome, Barrett's esophagus, gastroesophageal reflux disease, peptic ulcer, celiac disease, diverticulum, appendicitis, and biliary disease. The associations were stronger among women, individuals aged ≤ 60 years, and those with body mass index ≥ 25 kg/m2.CONCLUSIONS: This large-scale prospective cohort study revealed the associations of GIs with an increased risk of incident CVD, in particular CHD and PAD. These findings support the reinforced secondary CVD prevention among patients with gastrointestinal disorders.
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| 6. |
- Foox, Jonathan, et al.
(författare)
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The SEQC2 epigenomics quality control (EpiQC) study
- 2021
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Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and cross-validated resource for epigenetics research from the FDA’s Epigenomics Quality Control Group.ResultsEach sample is processed in multiple replicates by three whole-genome bisulfite sequencing (WGBS) protocols (TruSeq DNA methylation, Accel-NGS MethylSeq, and SPLAT), oxidative bisulfite sequencing (TrueMethyl), enzymatic deamination method (EMSeq), targeted methylation sequencing (Illumina Methyl Capture EPIC), single-molecule long-read nanopore sequencing from Oxford Nanopore Technologies, and 850k Illumina methylation arrays. After rigorous quality assessment and comparison to Illumina EPIC methylation microarrays and testing on a range of algorithms (Bismark, BitmapperBS, bwa-meth, and BitMapperBS), we find overall high concordance between assays, but also differences in efficiency of read mapping, CpG capture, coverage, and platform performance, and variable performance across 26 microarray normalization algorithms.ConclusionsThe data provided herein can guide the use of these DNA reference materials in epigenomics research, as well as provide best practices for experimental design in future studies. By leveraging seven human cell lines that are designated as publicly available reference materials, these data can be used as a baseline to advance epigenomics research.
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| 7. |
- Niu, Caoping, et al.
(författare)
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Configuration stability and physical properties of new diamondene structure
- 2023
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Ingår i: Materials Today Communications. - : Elsevier BV. - 2352-4928. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- The structure of monolayer diamond or diamondene based on bi-layer graphene through pressure conversion, combining characteristics of both graphene and diamond, has been confirmed theoretically and experimentally. In this work, by extending diamondene structure to the minimum repeating unit of bulk diamond along different crystallographic orientations, the configuration stability and physical properties of 21 kinds of diamondene were systematically investigated based on first-principles methods, and effects of hydrogen saturation were also presented. It was found that diamondene formed by compressing layered graphene would graphitize, and surface termination could prevent the graphitization. The electronic properties of diamondene can be adjusted by the concentration of H atoms with the bandgap varying from 0 eV to 3.45 eV, and some configurations exhibit ferromagnetism or anti-ferromagnetism. Moreover, diamondene has a high Young's modulus comparable to bulk diamond. Particularly, the configuration containing dumbbell units is twice as hard as diamond. The formation energies of all stable diamondene configurations were illustrated, and it was found that it is easier to synthesize diamondene by compressing few-layer graphene. Furthermore, the instability law of two-dimensional carbon structure was systematically discussed, which is important for designing new carbon allotropes.
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| 8. |
- Qin, Haihong, et al.
(författare)
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Design of overvoltage suppression filter based on high-frequency modeling of cable in SiC based motor drive
- 2022
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Ingår i: Energy Reports. - : Elsevier BV. - 2352-4847. ; 8, s. 822-831
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Tidskriftsartikel (refereegranskat)abstract
- SiC-based motor drives have the advantages of achieving higher efficiency and higher power density than traditional Si-based motor drives, and are gradually being widely used in electric power transmission. Due to different application situations such as oil field and airplane, a long cable is applied between the motor drive and three-phase motor and the distance may exceed hundreds of meters, which will cause serious voltage reflection problem, damaging working life of the motor. Meanwhile, the high slew rate of output voltage created by SiC-based motor drive deteriorates this phenomenon. In order to solve this problem, we first analyze the principle and influencing factors of voltage reflection, and establish the equivalent circuit model of the long cable. Then we put forward design method of LRC passive filter to suppress voltage reflection, and give simulation analysis. At last we built an experimental platform to verify the effectiveness of the LRC passive filter in SiC-based motor drive, and the experimental results show that the LRC passive filter with optimized parameters has good suppression effect of voltage reflection.
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| 9. |
- Qin, Haihong, et al.
(författare)
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Evaluation and Suppression Method of Turn-off Current Spike for SiC/Si Hybrid Switch
- 2023
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Ingår i: IEEE Access. - 2169-3536 .- 2169-3536. ; 11, s. 26832-26842
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Tidskriftsartikel (refereegranskat)abstract
- SiC MOSFET/Si IGBT (SiC/Si) hybrid switch usually selects the gate control pattern that SiC MOSFET turns on earlier and turns off later than Si IGBT, with the aim of making the hybrid switch show excellent switching characteristics of SiC MOSFET and reduce switching loss. However, when SiC MOSFET turns off, the fast slew rate of drain source voltage causes the current spike in Si IGBT due to the effects of parasitic capacitance charging and carrier recombination, which will produce additional turn-off loss, thus affecting the overall efficiency and temperature rise of the converter. Based on the double pulse test circuit of SiC/Si hybrid switch, the mathematical model of the turn-off transient process is established. The effects of the remnant carrier recombination degree of Si IGBT, the turn-off speed of SiC MOSFET and the working conditions on the turn-off current spike of hybrid switch are evaluated. Although adjusting these parameters can reduce the turn-off current spike somewhat, additional losses will be introduced. Therefore, a new method to suppress the turn-off current spike is proposed to balance the power loss and current stress.
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| 10. |
- Qin, Haihong, et al.
(författare)
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Evaluation of antiparallel SiC Schottky diode in SiC MOSFET phase-leg configuration of synchronous rectifier
- 2023
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Ingår i: Energy Reports. - 2352-4847. ; 9, s. 337-342
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Tidskriftsartikel (refereegranskat)abstract
- The MOSFET synchronous rectification (SR) is widely used to reduce the conduction loss during the freewheeling period. Due to the wide band gap of silicon carbide (SiC), the intrinsic body diode of SiC MOSFET exhibits a high voltage drop. Therefore, SiC Schottky diodes (SBD) and SiC MOSFETs are usually used in reverse parallel to reduce power loss. However, the increase of equivalent junction capacitance due to the addition of an external SiC SBD could bring larger turn-on current on opposite power transistor of the phase-leg. Furthermore, as the parasitic inductance associated with layout hinders the prompt transfer of current between SiC SBD and body diode, the external SiC SBD cannot be fully utilized, and it may deteriorate the overall performance, especially at heavy load. We comprehensively compare power losses when SiC SBD are antiparallel or not, at different working conditions, including different layout compactness, load current and dead time. It's hard to get the effect of loss reduction loss when add antiparallel SiC SBD due to the parasitic inductance induced by the layout. The results can provide a guidance to properly select SiC SBD in a phase-leg configuration under SR mode for freewheeling during the dead time.
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