| 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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| 11. |
- Qin, Haihong, et al.
(författare)
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Parameters Design and Optimization of SiC MOSFET Driving Circuit with Consideration of Comprehensive Loss and Voltage Stress
- 2023
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Ingår i: Micromachines. - : MDPI AG. - 2072-666X. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- In conventional parameters design, the driving circuit is usually simplified as an RLC second-order circuit, and the switching characteristics are optimized by selecting parameters, but the influence of switching characteristics on the driving circuit is not considered. In this paper, the insight mechanism for the gate-source voltage changed by overshoot and ringing caused by the high switching speed of SiC MOSFET is highlighted, and we propose an optimized design method to obtain optimal parameters of the SiC MOSFET driving circuit with consideration of parasitic parameters. Based on the double-pulse circuit, we evaluated the influence of main parameters on the gate-source voltage, including driving voltage, driving resistance, gate parasitic inductance, and stray inductance of the power circuit. A SiC-based boost PFC is constructed and tested. The test results show that the switching loss can be reduced by 7.282 W by using the proposed parameter optimization method, and the over-voltage stress of SiC MOSFET is avoided.
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| 12. |
- Ren, Luyao, et al.
(författare)
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Quartet DNA reference materials and datasets for comprehensively evaluating germline variant calling performance
- 2023
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Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome.RESULTS: We established a DNA reference material suite from four immortalized cell lines derived from a family of parents and monozygotic twins. Comprehensive reference datasets of 4.2 million small variants and 15,000 structural variants were integrated and certified for evaluating the reliability of germline variant calls inside the benchmark regions. Importantly, the genetic built-in-truth of the Quartet family design enables estimation of the precision of variant calls outside the benchmark regions. Using the Quartet reference materials along with study samples, batch effects are objectively monitored and alleviated by training a machine learning model with the Quartet reference datasets to remove potential artifact calls. Moreover, the matched RNA and protein reference materials and datasets from the Quartet project enables cross-omics validation of variant calls from multiomics data.CONCLUSIONS: The Quartet DNA reference materials and reference datasets provide a unique resource for objectively assessing the quality of germline variant calls throughout the whole-genome regions and improving the reliability of large-scale genomic profiling.
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| 13. |
- Shi, Wenming, et al.
(författare)
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Ambient PM2.5 and its chemical constituents on lifetime-ever pneumonia in Chinese children : A multi-center study
- 2021
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 146
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Tidskriftsartikel (refereegranskat)abstract
- The long-term effects of ambient PM2.5 and chemical constituents on childhood pneumonia were still unknown. A cross-sectional study was conducted in 30,315 children in the China Children, Homes, Health (CCHH) project, involving 205 preschools in six cities in China, to investigate the long-term effects of PM2.5 constituents on lifetime-ever diagnosed pneumonia. Information on the lifetime-ever pneumonia and demographics were collected by validated questionnaires. The lifetime annual average ambient PM2.5, ozone and five main PM2.5 constituents, including SO42-, NO3-, NH4+, organic matter (OM) and black carbon (BC), were estimated according to preschool addresses by a combination of satellite remote sensing, chemical transport modeling and ground-based monitors. The prevalence of lifetime-ever diagnosed pneumonia was 34.5% across six cities and differed significantly among cities (p = 0.004). The two-level logistic regression models showed that the adjusted odds ratio for PM2.5 (per 10 µg/m3) and its constituents (per 1 µg/m3)-SO42-, NO3-, NH4+, and OM were 1.12 (95% CI:1.07-1.18), 1.02 (1.00-1.04), 1.06 (1.04-1.09), 1.05 (1.03-1.07) and 1.09 (1.06-1.12), respectively. Children in urban area, aged < 5 years and breastfeeding time < 6 months enhanced the risks of pneumonia. Our study provided robust results that long-term levels of ambient PM2.5 and its constituents increased the risk of childhood pneumonia, especially NH4+, NO3- and OM.
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| 14. |
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| 15. |
- Shi, Wenming, et al.
(författare)
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Urinary phthalate metabolites in relation to childhood asthmatic and allergic symptoms in Shanghai
- 2018
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Ingår i: Environment International. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0160-4120 .- 1873-6750. ; 121, s. 276-286
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies can be found on phthalate exposure in relation to childhood asthma and allergic symptoms from Mainland China, where a persistent increase in prevalence of childhood asthma and allergic disease has been observed. Objectives: This study aimed to assess the exposure levels to phthalates and its relationship with asthmatic and allergic symptoms among children in Shanghai, which has the highest prevalence of childhood asthma in Mainland China. Methods: A follow-up study (2013-2014) of 434 children aged 5-10 years was conducted, based on the China, Children, Homes, Health (CCHH) study (2011-2012) in Shanghai, China. Information on asthmatic and allergic symptoms (wheeze, rhinitis, and eczema) were collected using validated questionnaires. Ten phthalate metabolites in morning urine samples were analyzed by high-performance liquid chromatography with triple quadrupole tandem mass spectrometry (HPLC-MS/MS). Multivariable logistic regression was used to estimate the associations between symptoms and urinary phthalate metabolites controlling for demographics, family history of allergic diseases and other covariates. Results: Nine out of 10 phthalate metabolites were detected in all subjects (average detection rate of 93.2%). By multivariable logistic regression analyses, the 4th quartile of Mono-n-butyl phthalate (MnBP) (reference: 1st quartile) had adjusted prevalence odds ratios (aPORs) and 95% confidence intervals (95%CIs) of 2.27(1.06-4.88), 2.14(1.02-4.46) and 2.98(1.19-7.50) for wheeze, rhinitis and eczema, respectively, while those of Mono-isobutyl phthalate (MiBP) were 2.23(1.08-4.62) and 2.96(1.02-8.60) for rhinitis and eczema, respectively. The highest quartile of mono-2-ethyl-5-hydroxyhexyl phthalate(MEHHP) and mono 2 ethyl 5 ox ohexyl phthalate(MEOHP) had aPORs and 95%CIs of 3.10(1.10-8.74) and 2.63(1.02-6.80) for eczema, respectively. By summing up the 4 low molecular weight metabolites (Sigma 4LMWP) and all 9 metabolites (Sigma(9)Total), the highest quartiles of Sigma 4LMWP and Sigma(9)Total were significantly associated with all symptoms. In most of the above associations, a significantly increasing trend from the 1st to the 4th quartile was observed. Subjects with 2 or 3 concomitant symptoms (reference: no symptoms) had significant positive associations with a higher level (the 4th quartile) of phthalate metabolites. Conclusions: Low MW metabolites such as MnBP and MiBP, high MW DEHP and the total amount of phthalate metabolites might have adverse health effects on asthma and allergic symptoms in Chinese children.
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| 16. |
- Yan, Jingjie, et al.
(författare)
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FENP : A Database of Neonatal Facial Expression for Pain Analysis
- 2023
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Ingår i: IEEE Transactions on Affective Computing. - : Institute of Electrical and Electronics Engineers (IEEE). - 1949-3045. ; 14:1, s. 245-254
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we introduce a new neonatal facial expression database for pain analysis. This database, called facial expression of neonatal pain (FENP), contains 11,000 neonatal facial expression images associated with 106 Chinese neonates from two children's hospitals, i.e., the Children's Hospital Affiliated to Nanjing Medical University and Second Affiliated Hospital Affiliated to Nanjing Medical University in China. The facial expression images cover four categories of facial expressions, i.e., severe pain expression, mild pain expression, crying expression and calmness expression, where each category contains 2750 neonatal facial expression images. Based on this database, we also investigate the pain facial expression recognition problem using several state-of-the-art facial expression features and expression recognition methods, such as Gabor+SVM, LBP+SVM, HOG+SVM, LBP+HOG+SVM, and several Convolutional Neural Network (CNN) methods (including AlexNet, VGGNet, GoogLeNet, ResNet and DenseNet). The experimental results indicate that the proposed neonatal pain facial expression database is very suitable for the study of both neonatal pain and facial expression recognition. Moreover, the FENP database is publicly available after signing a license agreement (the users can contact Jingjie Yan (yanjingjie@njupt.edu.cn), Guanming Lu (lugm@njupt.edu.cn)) or Xiaonan Li (xnli@njmu.edu.cn).
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| 17. |
- Zhong, Jun, et al.
(författare)
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A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer
- 2020
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 112:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
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