使用近红外光谱仪获取由高岭土、白云母和蒙脱石三种岩石矿物粉末混合成的模拟天然岩石样本的近红外漫反射光谱信息,通过标准归一化(standard normal variable)的方法对光谱数据进行预处理,采用随机森林(random forest)进行数学建模,对...使用近红外光谱仪获取由高岭土、白云母和蒙脱石三种岩石矿物粉末混合成的模拟天然岩石样本的近红外漫反射光谱信息,通过标准归一化(standard normal variable)的方法对光谱数据进行预处理,采用随机森林(random forest)进行数学建模,对岩石样本的组成成分进行预测,预测得到三种岩石成分最小均方根误差分别为:0.088 0,0.095 6,0.121 2。实验结果表明应用近红外漫反射光谱来测定天然岩石中各种矿物成分的含量是可行的,为今后岩石成分的快速检测提供了理论依据。展开更多
为探索用近红外光谱快速检测烤烟填充值的可行性,选取有代表性的94个河南烤烟样品,采用偏最小二乘法(Partial Least Square,PLS)将近红外光谱数据与其填充值的实测值进行拟合,建立填充值预测模型,考察了光谱预处理方法和光谱范围对建模...为探索用近红外光谱快速检测烤烟填充值的可行性,选取有代表性的94个河南烤烟样品,采用偏最小二乘法(Partial Least Square,PLS)将近红外光谱数据与其填充值的实测值进行拟合,建立填充值预测模型,考察了光谱预处理方法和光谱范围对建模效果的影响,并进行了内部交叉验证、外部验证和模型精度检验。结果表明:1标准正态变量变换(Standard normal variate,SNV)结合一阶导数法的光谱预处理方法和全谱范围适合构建填充值的近红外模型;2模型的决定系数达0.960,均方根校正误差(Root mean square error of calibration,RMSEC)为0.094,内部交叉验证和外部验证均表明模型预测值和实测值呈极显著相关;3模型精密度检验的相对标准偏差<3%。填充值近红外预测模型的重复性好,准确性较高,适于批量烤烟填充值的快速检测。展开更多
为了评判烟用接装纸内在质量稳定性,应用近红外光纤漫反射技术扫描烟用接装纸,对所得光谱进行标准正则变换(Standard Normal Variation,SNV)和一阶微分处理后,采用主成分分析(PrincipalComponent Analysis,PCA)法进行特征抽提,根据主成...为了评判烟用接装纸内在质量稳定性,应用近红外光纤漫反射技术扫描烟用接装纸,对所得光谱进行标准正则变换(Standard Normal Variation,SNV)和一阶微分处理后,采用主成分分析(PrincipalComponent Analysis,PCA)法进行特征抽提,根据主成分空间下的马氏距离建立校正集,对不同厂家烟用接装纸进行模式识别,并建立评价模型对相同厂家接装纸内在质量稳定性进行评判。结果表明,建立的校正集模型可有效识别不同厂家的烟用接装纸,评价模型对相同厂家接装纸内在质量稳定性的判别完全准确。展开更多
In a study published in Nature on June 10, researchers from Dr. YANG Hui’s Lab at the CAS Institute of Neuroscience (ION), and collaborators from the CAS-MPG Partner Institute for Computational Biology (PICB) and Sic...In a study published in Nature on June 10, researchers from Dr. YANG Hui’s Lab at the CAS Institute of Neuroscience (ION), and collaborators from the CAS-MPG Partner Institute for Computational Biology (PICB) and Sichuan University demonstrated that DNA base editors generated tens of thousands of off-target RNA single nucleotide variants (SNVs) and these off-target SNVs could be eliminated by introducing point mutations to the deaminases, built-in enzymes that act to rewrite the DNA bases.展开更多
Autism spectrum disorder(ASD)is a neurodevelopmental disorder with high genetic heritability but heterogeneity.Fully understanding its genetics requires whole-genome sequencing(WGS),but the ASD studies utilizing WGS d...Autism spectrum disorder(ASD)is a neurodevelopmental disorder with high genetic heritability but heterogeneity.Fully understanding its genetics requires whole-genome sequencing(WGS),but the ASD studies utilizing WGS data in Chinese population are limited.In this study,we present a WGS study for 334 individuals,including 112 ASD patients and their non-ASD parents.We identified 146 de novo variants in coding regions in 85 cases and 60 inherited variants in coding regions.By integrating these variants with an association model,we identified 33 potential risk genes(P<0.001)enriched in neuron and regulation related biological process.Besides the well-known ASD genes(SCN2A,NF1,SHANK3,CHD8 etc.),several high confidence genes were highlighted by a series of functional analyses,including CTNND1,DGKZ,LRP1,DDN,ZNF483,NR4A2,SMAD6,INTS1,and MRPL12,with more supported evidence from GO enrichment,expression and network analysis.We also integrated RNA-seq data to analyze the effect of the variants on the gene expression and found 12 genes in the individuals with the related variants had relatively biased expression.We further presented the clinical phenotypes of the proband carrying the risk genes in both our samples and Caucasian samples to show the effect of the risk genes on phenotype.Regarding variants in noncoding regions,a total of 74 de novo variants and 30 inherited variants were predicted as pathogenic with high confidence,which were mapped to specific genes or regulatory features.The number of de novo variants found in patient was significantly associated with the parents’ages at the birth of the child,and gender with trend.We also identified small de novo structural variants in ASD trios.The results in this study provided important evidence for understanding the genetic mechanism of ASD.展开更多
Single-nucleotide variants(SNVs)are crucial in disease development,but their accurate detection is challenging due to their low abundance and interference from wild-type targets.Although nucleic acid analogs like pept...Single-nucleotide variants(SNVs)are crucial in disease development,but their accurate detection is challenging due to their low abundance and interference from wild-type targets.Although nucleic acid analogs like peptide nucleic acids(PNAs)have been used for SNV detection,they often lack programmable sensitivity and specificity due to poorly calculated thermodynamics and kinetics.Here,we present a computational method for calculating the stacking energy of PNA and DNA hybrids,leveraging nearest neighbor parameters.Validation against experimental data from 16 sequences under varied hybridization conditions yielded good agreement using Bland-Altman analysis,with all data points falling within the confidence interval.Our findings indicate that PNA-DNA hybridization is thermodynamically more stable and exhibits kinetics 140-fold faster than DNA-DNA hybridization for identical sequences.Utilizing this computational framework,we designed PNA toehold probes,which were screened via simulations and experiments.This combined approach facilitated the identification of highly sensitive and specific PNA toehold probes for single point mutation detection via strand displacement reaction.Our results demonstrate the successful application of PNA toehold probes for detecting point mutations with high sensitivity and specificity,achieving a selective amplification of approximately 200-fold for variants with a variant allele frequency(VAF)of 0.5%using quantitative polymerase chain reaction.展开更多
Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor prognosis.However, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demo...Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor prognosis.However, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demonstrated. We performed single-cell whole exome sequencing to detect somatic singlenucleotide variants(SNVs) and significantly mutated genes(SMGs) among 34 tumor cells and 9 normal cells from a patient with GC. The Complete Prediction for Protein Conformation(CPPC) approach directly predicting the folding conformation of the protein 3D structure with Protein Folding Shape Code, combined with functional experiments were used to confirm the characterization of mutated SMGs in GC cells. We identified 201 somatic SNVs, including 117 non-synonymous mutations in GC cells. Further analysis identified 24 significant mutated genes(SMGs) in single cells, for which a single amino acid change might affect protein conformation. Among them, two genes(CDC27 and FLG) that were mutated only in single cells but not in the corresponding tumor tissue, were recurrently present in another GC tissue cohort, and may play a potential role to promote carcinogenesis, as confirmed by functional characterization. Our findings showed a mutational landscape of GC at intra-tumor level for the first time and provided opportunities for understanding the heterogeneity and individualized target therapy for this disease.展开更多
文摘为探索用近红外光谱快速检测烤烟填充值的可行性,选取有代表性的94个河南烤烟样品,采用偏最小二乘法(Partial Least Square,PLS)将近红外光谱数据与其填充值的实测值进行拟合,建立填充值预测模型,考察了光谱预处理方法和光谱范围对建模效果的影响,并进行了内部交叉验证、外部验证和模型精度检验。结果表明:1标准正态变量变换(Standard normal variate,SNV)结合一阶导数法的光谱预处理方法和全谱范围适合构建填充值的近红外模型;2模型的决定系数达0.960,均方根校正误差(Root mean square error of calibration,RMSEC)为0.094,内部交叉验证和外部验证均表明模型预测值和实测值呈极显著相关;3模型精密度检验的相对标准偏差<3%。填充值近红外预测模型的重复性好,准确性较高,适于批量烤烟填充值的快速检测。
基金National High-tech R&D Program(No.2013AA102507)National Natural Science Foundation of China(No.31001037 and No.31402142)+3 种基金Key Project of Ministry of Education of China(No.210180)Science and Technology Project of Chongqing Municipal Education Commission(No.KJ100627)NSC Grant from Taiwan(NSC-102-2621-B-029-002)National Undergraduate Training Programs for Innovation and Entrepreneurship(No.201410637005)
文摘为了评判烟用接装纸内在质量稳定性,应用近红外光纤漫反射技术扫描烟用接装纸,对所得光谱进行标准正则变换(Standard Normal Variation,SNV)和一阶微分处理后,采用主成分分析(PrincipalComponent Analysis,PCA)法进行特征抽提,根据主成分空间下的马氏距离建立校正集,对不同厂家烟用接装纸进行模式识别,并建立评价模型对相同厂家接装纸内在质量稳定性进行评判。结果表明,建立的校正集模型可有效识别不同厂家的烟用接装纸,评价模型对相同厂家接装纸内在质量稳定性的判别完全准确。
文摘In a study published in Nature on June 10, researchers from Dr. YANG Hui’s Lab at the CAS Institute of Neuroscience (ION), and collaborators from the CAS-MPG Partner Institute for Computational Biology (PICB) and Sichuan University demonstrated that DNA base editors generated tens of thousands of off-target RNA single nucleotide variants (SNVs) and these off-target SNVs could be eliminated by introducing point mutations to the deaminases, built-in enzymes that act to rewrite the DNA bases.
基金supported by the National Program for Brain Science and Brain-like Intelligence Technology of China (2021ZD0200800)Beijing Municipal Science and Technology Commission (Z181100001518005)+1 种基金the National Natural Science Foundation of China (31401139, 32170613, 81671358, 81873803)the Natural Science Foundation of Beijing Municipality (7232225)
文摘Autism spectrum disorder(ASD)is a neurodevelopmental disorder with high genetic heritability but heterogeneity.Fully understanding its genetics requires whole-genome sequencing(WGS),but the ASD studies utilizing WGS data in Chinese population are limited.In this study,we present a WGS study for 334 individuals,including 112 ASD patients and their non-ASD parents.We identified 146 de novo variants in coding regions in 85 cases and 60 inherited variants in coding regions.By integrating these variants with an association model,we identified 33 potential risk genes(P<0.001)enriched in neuron and regulation related biological process.Besides the well-known ASD genes(SCN2A,NF1,SHANK3,CHD8 etc.),several high confidence genes were highlighted by a series of functional analyses,including CTNND1,DGKZ,LRP1,DDN,ZNF483,NR4A2,SMAD6,INTS1,and MRPL12,with more supported evidence from GO enrichment,expression and network analysis.We also integrated RNA-seq data to analyze the effect of the variants on the gene expression and found 12 genes in the individuals with the related variants had relatively biased expression.We further presented the clinical phenotypes of the proband carrying the risk genes in both our samples and Caucasian samples to show the effect of the risk genes on phenotype.Regarding variants in noncoding regions,a total of 74 de novo variants and 30 inherited variants were predicted as pathogenic with high confidence,which were mapped to specific genes or regulatory features.The number of de novo variants found in patient was significantly associated with the parents’ages at the birth of the child,and gender with trend.We also identified small de novo structural variants in ASD trios.The results in this study provided important evidence for understanding the genetic mechanism of ASD.
基金support from the National Key R&D Program of China(2021YFF1200300)the National Natural Science Foundation of China(Nos.22174094,22274097)+1 种基金the Fundamental Research Funds for the Central Universities(YG2023QNA33)Young Leading Scientists Cultivation Plan supportedby ShanghaiMunicipal Education Commission(ZXWH1082101).
文摘Single-nucleotide variants(SNVs)are crucial in disease development,but their accurate detection is challenging due to their low abundance and interference from wild-type targets.Although nucleic acid analogs like peptide nucleic acids(PNAs)have been used for SNV detection,they often lack programmable sensitivity and specificity due to poorly calculated thermodynamics and kinetics.Here,we present a computational method for calculating the stacking energy of PNA and DNA hybrids,leveraging nearest neighbor parameters.Validation against experimental data from 16 sequences under varied hybridization conditions yielded good agreement using Bland-Altman analysis,with all data points falling within the confidence interval.Our findings indicate that PNA-DNA hybridization is thermodynamically more stable and exhibits kinetics 140-fold faster than DNA-DNA hybridization for identical sequences.Utilizing this computational framework,we designed PNA toehold probes,which were screened via simulations and experiments.This combined approach facilitated the identification of highly sensitive and specific PNA toehold probes for single point mutation detection via strand displacement reaction.Our results demonstrate the successful application of PNA toehold probes for detecting point mutations with high sensitivity and specificity,achieving a selective amplification of approximately 200-fold for variants with a variant allele frequency(VAF)of 0.5%using quantitative polymerase chain reaction.
基金supported by the National Key Research and Development Program of China (2017YFC1308900)Beijing Municipal Commission of Health and Family Planning Project (PXM2018_026279_000005)+1 种基金National High-tech R&D Program of China (2012AA02A203, No.2012AA02A504)Beijing talent fund
文摘Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor prognosis.However, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demonstrated. We performed single-cell whole exome sequencing to detect somatic singlenucleotide variants(SNVs) and significantly mutated genes(SMGs) among 34 tumor cells and 9 normal cells from a patient with GC. The Complete Prediction for Protein Conformation(CPPC) approach directly predicting the folding conformation of the protein 3D structure with Protein Folding Shape Code, combined with functional experiments were used to confirm the characterization of mutated SMGs in GC cells. We identified 201 somatic SNVs, including 117 non-synonymous mutations in GC cells. Further analysis identified 24 significant mutated genes(SMGs) in single cells, for which a single amino acid change might affect protein conformation. Among them, two genes(CDC27 and FLG) that were mutated only in single cells but not in the corresponding tumor tissue, were recurrently present in another GC tissue cohort, and may play a potential role to promote carcinogenesis, as confirmed by functional characterization. Our findings showed a mutational landscape of GC at intra-tumor level for the first time and provided opportunities for understanding the heterogeneity and individualized target therapy for this disease.
