| 1. |
- 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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| 2. |
- 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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| 3. |
- Gao, Ruo Bin, et al.
(författare)
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A Wideband Co-Linearly Polarized Composite Antenna with High Isolation
- 2023
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Ingår i: IEEE Antennas and Wireless Propagation Letters. - 1536-1225. ; , s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a high-isolation two-port co-linearly polarized (co-LP) composite antenna is proposed. Dipole and W8JK array modes with co-LP omnidirectional patterns can be simultaneously supported by a plate with two etched back-to-back tapered slots. A microstrip differential and a T-divider coupling feeding networks are developed to selectively excite the dipole and W8JK modes, which results in a high isolation and low correlation between two co-LP ports without using any decoupling structures. Reflecting ground is applied to realize the directional radiation. Measurement results show that the overlapped operating band of the antenna can cover 3.4 - 4.1 GHz with low measured envelope correlation coefficients (< 2.5 × 10-3) and high isolation (> 20 dB). Dual-polarized four-port element with good performances can be easily obtained based on the proposed co-LP antenna. The simulated results of the four-port prototype indicate that the proposed antenna is a promising candidate for the future compact massive MIMO array antenna.
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| 4. |
- Li, Jiang, et al.
(författare)
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SGLT2 inhibition, circulating metabolites, and atrial fibrillation : a Mendelian randomization study
- 2023
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Ingår i: Cardiovascular Diabetology. - : BioMed Central (BMC). - 1475-2840. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors have shown promise in reducing the risk of atrial fibrillation (AF). However, the results are controversial and the underlying metabolic mechanism remains unclear. Emerging evidence implied that SGLT2 inhibitors have extra beneficial metabolic effects on circulating metabolites beyond glucose control, which might play a role in reducing the risk of AF. Hence, our study aimed to investigate the effect of circulating metabolites mediating SGLT2 inhibition in AF by Mendelian randomization (MR).MethodsA two-sample and two-step MR study was conducted to evaluate the association of SGLT2 inhibition with AF and the mediation effects of circulating metabolites linking SGLT2 inhibition with AF. Genetic instruments for SGLT2 inhibition were identified as genetic variants, which were both associated with the expression of SLC5A2 gene and glycated hemoglobin level (HbA1c). Positive control analysis on type 2 diabetes mellitus (T2DM) was conducted to validate the selection of genetic instruments.ResultsGenetically predicted SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of T2DM (odds ratio [OR] = 0.63 [95% CI 0.45, 0.88], P = 0.006) and AF (0.51 [0.27, 0.97], P = 0.039). Among 168 circulating metabolites, two metabolites were both associated with SGLT2 inhibition and AF. The effect of SGLT2 inhibition on AF through the total concentration of lipoprotein particles (0.88 [0.81, 0.96], P = 0.004) and the concentration of HDL particles (0.89 [0.82, 0.97], P = 0.005), with a mediated proportion of 8.03% (95% CI [1.20%, 14.34%], P = 0.010) and 7.59% ([1.09%, 13.34%], P = 0.011) of the total effect, respectively.ConclusionsThis study supported the association of SGLT2 inhibition with a reduced risk of AF. The total concentration of lipoprotein particles and particularly the concentration of HDL particles might mediate this association. Further mechanistic and clinical studies research are needed to understand the mediation effects of circulating metabolites especially blood lipids in the association between SGLT2 inhibition and AF.
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| 5. |
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| 6. |
- Sun, Ying, et al.
(författare)
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Association between Life's Essential 8 score and risk of premature mortality in people with and without type 2 diabetes : A prospective cohort study.
- 2023
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 39:5
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To evaluate the association of cardiovascular health (CVH), measured by Life's Essential 8 score, with the risk of premature mortality and to determine the patterns of CVH-related differences in life expectancy among people with and without type 2 diabetes (T2D).MATERIALS AND METHODS: This prospective study included 309,789 participants (age 56.6 ± 8.1 years; 46% men) enroled in the UK Biobank. The Life's Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (BMI, non-HDL cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH was categorised into low, moderate, and high groups. Premature death was defined as death before the age of 75. Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and life expectancy was estimated.RESULTS: During a median follow-up of 12.7 years, 13,683 cases of premature death were documented. Compared to participants with low CVH, the multivariable HRs (95% CIs) of premature death were 0.59 (0.56-0.62) and 0.42 (0.39-0.45) for the moderate and high CVH groups, respectively. This association was stronger in participants with T2D compared with those without T2D. At the age of 50 years, compared to low CVH groups, high CVH was associated with a gain of 9.79 (9.70-9.87) and 5.58 (5.48-5.67) additional life years for men with and without T2D, respectively. The corresponding life gain for women with and without T2D was 24.21 (24.13-24.27) and 10.18 (10.10-10.27), respectively.CONCLUSIONS: Maintaining an ideal Life's Essential 8 score may provide more benefits for people with T2D than for those without T2D, including a lower risk of premature death and an increased lifespan.
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| 7. |
- Sun, Ying, et al.
(författare)
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Associations of Sugar-Sweetened Beverages, Artificially Sweetened Beverages, and Pure Fruit Juice With Nonalcoholic Fatty Liver Disease : Cross-sectional and Longitudinal Study
- 2023
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Ingår i: Endocrine Practice. - : Elsevier. - 1530-891X .- 1934-2403. ; 29:9, s. 735-742
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Forskningsöversikt (refereegranskat)abstract
- ObjectiveWe aimed to test the associations of sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), and pure fruit juice (PJ) consumption with the risk of nonalcoholic fatty liver disease (NAFLD).MethodsData for 136 277 UK Biobank participants who completed the dietary questionnaire and did not have a history of liver disease were included. Logistic regression was used for the cross-sectional setting where NAFLD was defined by a fatty liver index (FLI) ≥60. Cox proportional hazard regression was used for the longitudinal setting where hospitalized NAFLD was defined as hospital admission with Internationl Classification of Diseases-10 codes K76.0 and K75.8.ResultsCompared with 0 L/wk for corresponding beverages, multivariate-adjusted odds ratios (95% confidence intervals) for NAFLD in consumption ≤1, 1 to 2, and >2 L/wk were 1.06 (1.02-1.10), 1.24 (1.19-1.29), and 1.42 (1.35-1.49) for SSB; 1.43 (1.37-1.50), 1.73 (1.65-1.82), and 2.37 (2.25-2.50) for ASB, and 0.87 (0.84-0.89), 0.91 (0.88-0.94), and 1.07 (1.02-1.13) for PJ, respectively. Consumption of SSB and ASB were both positively correlated with FLI (P for line < .001). During a median follow-up of 10.2 years, 1043 cases of hospitalized NAFLD were recorded. ASB consumption of 1 to 2 and >2 L/wk was associated with a 22% (0.99-1.50) and 35% (1.11-1.65) increased risk of hospitalized NAFLD, respectively (P for trend = .002). However, the associations of SSB and PJ with the risk of hospitalized NAFLD were not significant.ConclusionsConsumption of SSB, ASB, and PJ were all related to the risk of NAFLD. Excessive consumption of ASBs was associated with an increased risk of incident hospitalized NAFLD.
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| 8. |
- Sun, Ying, et al.
(författare)
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Birth weight, ideal cardiovascular health metrics in adulthood, and incident cardiovascular disease
- 2024
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Ingår i: Chinese Medical Journal. - : Wolters Kluwer. - 0366-6999. ; 137:10, s. 1160-1168
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods: In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results: Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5–4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00–1.16) in men and 1.23 (1.16–1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age (P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0–1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01–5.13] in men; 4.24 [3.33–5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17–1.58]) could be decomposed into 24.7% (95% CI: 15.0%–34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%–72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%–18.6%) for their additive interaction in women.Conclusions: Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.
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| 9. |
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| 10. |
- Sun, Ying, et al.
(författare)
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Joint exposure to positive affect, life satisfaction, broad depression, and neuroticism and risk of cardiovascular diseases : A prospective cohort study
- 2022
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 359, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Psychologic wellbeing can impact cardiovascular health. We aimed to evaluate the joint association of multiple psychologic wellbeing factors with cardiovascular diseases (CVD) and examine whether this association was modified by genetic susceptibility. Methods: In the UK Biobank, 126,255 participants free of CVD (coronary heart disease [CHD], stroke, and heart failure [HF]) at baseline, who completed a questionnaire on psychological factors, were included. The psychological wellbeing score was calculated by four factors: happiness, life satisfaction, broad depression, and neuroticism. Cox proportional hazard models were used to assess the association between the psychological wellbeing score and CVD risk. Results: During the median follow-up of 11.5 years, 10,815 participants had newly diagnosed CVDs. Low life satisfaction, the presence of depression, and neuroticism score >= 1 were significantly associated with an increased risk of CVD in the multivariable-adjusted model. Through decreasing the psychological wellbeing score, there were significant increasing linear trends in the risk of CVD, CHD, stroke, and HF (all p for trend < 0.001). Participants with the lowest psychological wellbeing score had the highest risk for CVD (HR 1.51, 95% CI 1.42-1.61). Women were more susceptible to worse psychological wellbeing status for CVD than men (p for interaction = 0.009). The associations of the psychological wellbeing score with CVD were consistent across genetic risk (p for interaction >0.05). When considered jointly, participants exposed to high-risk psychological wellbeing and genetic status had a 2.70-fold (95% CI 2.25-3.24) risk for CHD. Conclusions: Joint exposure to multiple psychological wellbeing factors was associated with increased risks of incident CVD in an additive manner, regardless of genetic susceptibility.
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