Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) datas...Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment.展开更多
The rhesus macaque(Macaca mulatta)is a crucial experimental animal that shares many genetic,brain organizational,and behavioral characteristics with humans.A macaque brain atlas is fundamental to biomedical and evolut...The rhesus macaque(Macaca mulatta)is a crucial experimental animal that shares many genetic,brain organizational,and behavioral characteristics with humans.A macaque brain atlas is fundamental to biomedical and evolutionary research.However,even though connectivity is vital for understanding brain functions,a connectivity-based whole-brain atlas of the macaque has not previously been made.In this study,we created a new whole-brain map,the Macaque Brainnetome Atlas(MacBNA),based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data.The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections.The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images.As a demonstrative application,the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure.The resulting resource includes:(1)the thoroughly delineated Macaque Brainnetome Atlas(MacBNA),(2)regional connectivity profiles,(3)the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset(Brainnetome-8),and(4)multi-contrast MRI,neuronal-tracing,and histological images collected from a single macaque.MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function.Therefore,it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.展开更多
传统无损压缩算法对屏幕图像的压缩效果不佳。该文根据典型屏幕图像的特性,以LZ4HC(LZ4 High Compression)算法为具体实现基础,提出一种基于串匹配的高性能低复杂度(String Matching with High Performance and Low Complexity,SMHPLC)...传统无损压缩算法对屏幕图像的压缩效果不佳。该文根据典型屏幕图像的特性,以LZ4HC(LZ4 High Compression)算法为具体实现基础,提出一种基于串匹配的高性能低复杂度(String Matching with High Performance and Low Complexity,SMHPLC)的屏幕图像无损压缩算法。相对于传统字典编码无损压缩算法,新算法提出了以像素为搜索和匹配单位,对未匹配串长度、匹配串长度以及匹配偏移量这3个编码参数进行联合优化编码,并对参数进行映射编码。实验结果表明,SMHPLC具有高性能和低复杂度的综合优势,大幅降低编码复杂度,提高了编码效率。使用移动的文字和图形类的AVS2通用测试序列作为测试对象,对于YUV和RGB两种格式,SMHPLC算法比LZ4HC总体节省码率分别为22.4%,21.2%,同时编码复杂度降低分别为35.5%,46.8%。展开更多
基金supported by the grants from the Major State Basic Research Development Program of China(2012CB517902 and 2012CB517904)National Key Technology Research and Development Program of China(2012BAI03B00)+3 种基金Special Research Program of National Health and Family Planning Commission of China(201302002)International S&T Cooperation Program of China(2011DFA30670)National Natural Science Foundation of China(31571357/31771404)supported in part by research funding from AstraZeneca Innovation Center China and Wenzhou Medical University
文摘Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment.
基金partially supported by the Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project(2021ZD0200200)the National Natural Science Foundation of China(62327805,82151307,82072099,82202253)。
文摘The rhesus macaque(Macaca mulatta)is a crucial experimental animal that shares many genetic,brain organizational,and behavioral characteristics with humans.A macaque brain atlas is fundamental to biomedical and evolutionary research.However,even though connectivity is vital for understanding brain functions,a connectivity-based whole-brain atlas of the macaque has not previously been made.In this study,we created a new whole-brain map,the Macaque Brainnetome Atlas(MacBNA),based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data.The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections.The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images.As a demonstrative application,the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure.The resulting resource includes:(1)the thoroughly delineated Macaque Brainnetome Atlas(MacBNA),(2)regional connectivity profiles,(3)the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset(Brainnetome-8),and(4)multi-contrast MRI,neuronal-tracing,and histological images collected from a single macaque.MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function.Therefore,it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.
基金supported by the National Natural Science Foundation of China(32271545 and 31972030)Major Program of Haihe Laboratory of Synthetic Biology(22HHSWSS00016 and 22HHSWSS00003)+2 种基金Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-008-03 and TSBICIP-PTJJ-007-10)Youth Promotion Association of Chinese Academy of Sciences(CAS)(2021176)CAS Project for Young Scientists in Basic Research(YSBR-072)。
文摘传统无损压缩算法对屏幕图像的压缩效果不佳。该文根据典型屏幕图像的特性,以LZ4HC(LZ4 High Compression)算法为具体实现基础,提出一种基于串匹配的高性能低复杂度(String Matching with High Performance and Low Complexity,SMHPLC)的屏幕图像无损压缩算法。相对于传统字典编码无损压缩算法,新算法提出了以像素为搜索和匹配单位,对未匹配串长度、匹配串长度以及匹配偏移量这3个编码参数进行联合优化编码,并对参数进行映射编码。实验结果表明,SMHPLC具有高性能和低复杂度的综合优势,大幅降低编码复杂度,提高了编码效率。使用移动的文字和图形类的AVS2通用测试序列作为测试对象,对于YUV和RGB两种格式,SMHPLC算法比LZ4HC总体节省码率分别为22.4%,21.2%,同时编码复杂度降低分别为35.5%,46.8%。
