Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

图像抠图与copy-paste结合的数据增强方法

提出一种基于图像抠图与copy-paste结合的数据增强方法(matting-paste),采用图像抠图法获取单个垃圾实例的准确轮廓,并对单个实例进行旋转和亮度变换.根据物体轮廓信息,把实例粘贴到背景图上,无需额外的人工标注即可生成新的带有标注的数据,从而提高数据集的多样性和复杂性.结果表明:数据集扩充后的mask比数据集扩充前的识别精度提高了0.039,matting-paste能在已有数据集上有效地扩充数据,进一步提高模型的识别精度.

De novel heterozygous copy number deletion on 7q31.31-7q31.32 involving TSPAN12 gene with familial exudative vitreoretinopathy in a Chinese family

AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.

Copy number variation of B1 controls awn length in wheat

Wheat awns contribute to photosynthesis and grain production.In this study,an F2population and F2:3families from a cross between the awned line 7D12 and the Chinese awnless variety Shiyou 20(SY20)were used to identify loci associated with awn length.Bulked-segregant RNA sequencing and linkage mapping identified a single dominant locus in a 0.3 cM interval on chromosome 5AL.Five genes were in the interval,including the recently cloned awn inhibitor B1.Although a single copy of the B1 gene was detected in 7D12,SY20 carried five copies of the gene.Increased copy number of B1 in SY20enhanced gene expression.Based on sequence variation among the promoter regions of five B1 gene copies in SY20,two dominant markers were developed and found to cosegregate with B1 in a population of 931 wheat accessions.All 77 awnless accessions harbored sequence variations in the B1 promoter regions similar to those of SY20 and thus carried multiple copies of the gene,whereas 15 randomly selected awned wheats carried only one copy.These results suggest that an increase in copy number of the B1 gene is associated with inhibition of awn length.

Benchmark Dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects

Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a biomarker.Methods A total of 782 subjects were recruited,including 238 controls and 544 exposed workers.The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction.Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95%confidence lower limit(BMDL).Results The mtDNAcn of the exposure group was lower than that of the control group(0.60±0.29 vs.1.03±0.31;P<0.001).A dose-response relationship was shown between the mtDNAcn damage and COEs.Using the Benchmark Dose Software,the occupational exposure limits(OELs)for COEs exposure in males was 0.00190 mg/m^(3).The OELs for COEs exposure using the BBMD were 0.00170 mg/m^(3)for the total population,0.00158 mg/m^(3)for males,and 0.00174 mg/m^(3)for females.In possible risk obtained from animal studies(PROAST),the OELs of the total population,males,and females were 0.00184,0.00178,and 0.00192 mg/m^(3),respectively.Conclusion Based on our conservative estimate,the BMDL of mitochondrial damage caused by COEs is0.002 mg/m^(3).This value will provide a benchmark for determining possible OELs.

Metaheuristics with Optimal Deep Transfer Learning Based Copy-Move Forgery Detection Technique

The extensive availability of advanced digital image technologies and image editing tools has simplified the way of manipulating the image content.An effective technique for tampering the identification is the copy-move forgery.Conventional image processing techniques generally search for the patterns linked to the fake content and restrict the usage in massive data classification.Contrast-ingly,deep learning(DL)models have demonstrated significant performance over the other statistical techniques.With this motivation,this paper presents an Optimal Deep Transfer Learning based Copy Move Forgery Detection(ODTL-CMFD)technique.The presented ODTL-CMFD technique aims to derive a DL model for the classification of target images into the original and the forged/tampered,and then localize the copy moved regions.To perform the feature extraction process,the political optimizer(PO)with Mobile Networks(MobileNet)model has been derived for generating a set of useful vectors.Finally,an enhanced bird swarm algorithm(EBSA)with least square support vector machine(LS-SVM)model has been employed for classifying the digital images into the original or the forged ones.The utilization of the EBSA algorithm helps to properly modify the parameters contained in the Multiclass Support Vector Machine(MSVM)technique and thereby enhance the classification performance.For ensuring the enhanced performance of the ODTL-CMFD technique,a series of simulations have been performed against the benchmark MICC-F220,MICC-F2000,and MICC-F600 datasets.The experimental results have demonstrated the improvised performance of the ODTL-CMFD approach over the other techniques in terms of several evaluation measures.

Copy number variation sequencing for diagnosis of cytomegalovirus infection based low-depth whole-genome sequencing technology in fetus:Three cases and literature review

Objective:To summarize the application value of copy number variant sequencing(CNV-seq)in the detection of fetal chromosome and cytomegalovirus load.Methods:The study analyzed the clinical basic data,relevant laboratory tests,treatment process,and outcomes of three patients with positive cytomegalovirus load detected by CNV-seq for fetal chromosomes and cytomegalovirus load,and literature review was done simutaneoubly.Results:In all three cases,the amniotic fluid cytomegalovirus load was less than 105 Copies/ml,and there were no significant neurological abnormalities observed during pregnancy or postpartum follow-up.There is no literature review on the application of CNV-seq technology in the detection of cytomegalovirus infection,only literature reports on genome analysis of CMV-DNA in confirmed patients were available.Conclusion:CNV-seq can be used to detect cytomegalovirus load,which may have a certain degree of predictive value for fetal outcome.CNV-seq can simultaneously detect fetal chromosomes and pathogenic microorganisms,which is of great significance for the prevention and control of birth defects.

基于改进显著图和局部特征匹配的copy-move窜改检测

检测整幅窜改图像的方法增加了许多非必要的计算量,为了降低计算复杂度和进一步提高检测精确率,提出了一种基于改进显著图和局部特征匹配的copy-move窜改检测方法。首先,结合图像梯度改进显著图,分离出包含图像高纹理信息的局部显著区域;其次,只对该局部区域采用SIFT(scale invariant feature transform)算法提取特征点;然后,对显著性小的图像采用密度聚类和二阶段匹配策略,对显著性大的图像采用超像素分割和显著块特征匹配的策略;最后,结合PSNR和形态学操作来定位窜改区域。在两个公开数据集上进行实验,该方法的平均检测时间小于10 s,平均检测精确率大于97%,均优于所对比的方法。实验结果表明,该方法能够大幅缩减检测时间、有效提高检测精确率,并且对几何变换和后处理操作也都具有较好的鲁棒性。

基于知识增强的开放域多轮对话模型

如何减轻安全回复和重复回复一直是开放域多轮对话模型的两大挑战性难题.然而,现有开放域对话模型往往忽略了对话目标的引导性作用,以及如何在对话历史和对话目标中引入和选择更精确的知识信息.鉴于此,提出基于知识增强的多轮对话模型.所提模型首先将对话历史中实词进行义原及领域词替换,达到消除歧义和丰富对话文本表示的效果.然后将经过知识增强后的对话历史、扩充的三元组世界知识、知识管理和知识拷贝加以集成,以融合知识、词汇、对话历史和对话目标多种信息,生成多样性回复.通过两个国际基准开放域汉语对话语料库上的实验结果及可视化验证所提模型同时在自动评测和人工评测上的有效性.

胎儿末端染色体非平衡易位遗传方式的CNV-seq联合G显带核型分析

目的:通过拷贝数变异检测(CNV-seq)联合G显带核型分析对产前诊断和流产的胎儿末端染色体非平衡易位发生频率以及遗传方式进行分析。方法:选取2018年6月至2021年12月在郑州大学第一附属医院经CNV-Seq判定为末端染色体非平衡易位的病例,采用外周血G显带核型分析或FISH检测对胎儿父母进行溯源分析。结果:17248例产前诊断和流产病例中,88例检出末端染色体非平衡易位,检出率为0.51%。其中59例行父母G显带核型分析或FISH检测,32例(54.24%)是由于父母为平衡易位导致,27例(45.76%)为新发变异。结论:诊断为末端染色体非平衡易位的病例,父母行G显带核型分析或FISH检测可提高染色体平衡易位携带者的检出率。

“Mimēsis”的辩证法:阿多诺对“技术”的媒介美学批判

在阿多诺针对大众媒介技术展开的现代美学批判中,“Mimēsis”(摹仿)的辩证法是核心向度之一。在对本雅明关于技术复制与现代艺术命运关系之思考的容受中,通过指认技术复制是“摹仿的绝对化”而真正艺术是“摹仿行为的庇护所”,阿多诺揭示了“摹仿”在技术时代的美学中仍然能够作为一个批判概念得以存留的可能性和必要性。其根本原因在于:作为摹仿绝对化的技术复制无论其表面上多么繁荣多样,其实质只是“重复”;但如果媒介技术的“复制”功能成为技术时代艺术的重要摹仿对象,在生产差异之“重复”的“摹仿辩证法”中,复制的技术便可以被艺术的摹仿技艺所吸收转化,从而实现技术的美学“救赎”。

全外显子测序联合基因组拷贝数变异测序在儿科遗传病诊断中的应用

目的探讨全外显子测序(whole exome sequencing,WES)联合基因组拷贝数变异测序(copy number variation sequencing,CNVseq)在儿科遗传病诊断中的应用价值。方法选取2019年8月至2023年7月郑州市妇幼保健院新生儿科及儿科收治的怀疑患有遗传性疾病或临床诊断不明确的患儿为研究对象,采集患儿及其父母外周血进行WES及CNVseq检测,对检出的变异进行分类及评级,并进行一代测序或qPCR验证。结果共纳入患儿33例,其中男性18例,女性15例,年龄范围为1 d~8岁。WES的阳性检出率为36.4%(12/33),CNVseq阳性检出率为9.1%(3/33),两者联合阳性检出率为45.5%(15/33)。结论WES联合CNVseq是儿童遗传性疾病分子诊断的有力工具,可作为一线检测手段在临床大力推广。

《梅氏缀玉轩剧目》考论

考索梅兰芳能演和已演剧目是研究梅兰芳表演艺术的重要课题,但因缺乏全面准确的记载,加之统计方法有异,故人言人殊。新发现梅兰芳纪念馆藏有《梅氏缀玉轩剧目》抄本一册,其著录的105个剧目大部分是梅兰芳的演出剧目,有些则是能演而未演的剧目。著录者不是梅兰芳本人,很可能是著有《梅屑》一文的亚庸。其著录的最后一个剧目《花蕊夫人》,有人认为是尚小云所编演,但其问世早于尚小云编演的同名剧目。《梅氏缀玉轩剧目》未著录1927年12月26日在北平首演的古装新戏《俊袭人》,据此可推断其写定时间在1927年底之前。《梅氏缀玉轩剧目》出自梅兰芳故居,著录虽有遗漏,但它是当时著录梅氏能演和已演剧目最多的文献,既可从中一窥20世纪二三十年代青年梅兰芳超群的艺术功力,亦可见我国戏曲史由以剧作家和文本为中心向以演员和舞台表演为中心转型之新变。

884例性染色体异常胎儿产前诊断结果分析

目的 对884例无创产前筛查(NIPS)提示性染色体异常的羊水样本进行核型分析、荧光原位杂交技术(FISH)和拷贝数变异测序(CNV-seq)检测,探讨不同方法在产前诊断中的价值。方法 选取2015年1月—2022年12月天津市中心妇产科医院孕早期NIPS提示胎儿为性染色体异常的孕妇884例,于孕中期采集羊水样本,进行羊水细胞核型分析和FISH检测,对结果不一致或培养失败的样本进一步行CNV-seq检测。结果 884例孕妇中,有341例(38.6%)检出异常核型,11例(1.2%)羊水细胞培养失败。NIPS性染色体阳性预测值为39.2%(341/873)。341例核型分析异常样本中,最常见的核型异常类型是47,XXY(108例),其次为47,XXX(80例)、47,XYY(68例)、45,X(18例),共检出51例嵌合体。884例孕妇中,有862例FISH检测结果与核型分析或CNV-seq结果一致,FISH的阳性预测值为97.5%;24例与核型分析结果不一致,进一步行CNV-seq检测,有22例CNV-seq结果与核型分析结果一致,并能相互补充分析;2例不一致样本中,1例核型分析结果为46,~+mar,FISH和CNV-seq结果均为45,X;1例核型分析结果为嵌合Y染色体异染色质区缺失,FISH和CNV-seq结果均为嵌合体,结构未见异常。结论 NIPS提示性染色体异常时,建议首选FISH和核型分析联合检测,可快速、准确地诊断染色体异常。对于疑似染色体特殊结构异常,建议进行FISH、核型分析和CNV-seq联合检测,可明确遗传学病因。

基于组合加权k近邻分类的无线传感网络节点复制攻击检测方法

无线传感网络节点体积小,隐蔽性强,节点复制攻击检测的难度较大,为此提出一种基于组合加权k近邻分类的无线传感网络节点复制攻击检测方法。通过信标节点的空间位置数据与相距跳数得出各节点之间的相似程度,结合高斯径向基核函数求解未知节点的横轴、纵轴的空间坐标,确定各网络节点的空间位置;根据网络节点的属性特征与投票机制建立节点复制攻击模型,凭借组合加权k近邻分类法划分节点类型,并将结果传送至簇头节点,由簇头节点做出最后的仲裁,识别出节点复制攻击行为。仿真结果表明,所提方法的节点复制攻击检测率最大值为99.5%,最小值为97.9%,对节点复制攻击检测的耗时为5.41 s,通信开销数据包数量最大值为209个,最小值为81个。

基于实体复制和双粒度指导的抽象摘要

抽象神经网络在文本摘要领域取得了长足进步,展示了令人瞩目的成就.然而,由于抽象摘要的灵活性,它很容易造成生成的摘要忠实性差的问题,甚至偏离源文档的语义主旨.针对这一问题,本文提出了两种方法来提高摘要的保真度.(1)由于实体在摘要中起着重要作用,而且通常来自于原始文档,因此本文提出允许模型从源文档中复制实体,确保生成的实体与源文档中的实体相匹配,这有助于防止生成不一致的实体.(2)为了更好地防止生成的摘要与原文产生语义偏离,本文在摘要生成过程中使用关键实体和关键token作为两种不同粒度的指导信息以指导摘要的生成.本文使用ROUGE指标在两个广泛使用的文本摘要数据集CNNDM和XSum上评估了本文方法的性能,实验结果表明,这两种方法在提高模型性能方面都取得了显著的效果.此外,实验还证明了实体复制机制可以在一定程度上借助指导信息以纠正引入的语义噪声.

子宫内膜癌分子分型应用及临床意义

目的分析子宫内膜癌分子分型的应用与临床意义。方法选取本院40例子宫内膜癌患者为研究对象。对其开展常规病理与免疫组织化学染色切片,分析分子分型分布情况。结果40例患者中,高拷贝型、低拷贝型、MSI-H型、POLE超突变型各占11例、20例、7例、2例,其中子宫内膜样腺癌共计33例,而高拷贝型、低拷贝型、MSI-H型、POLE超突变型各占6例、19例、6例、2例。非子宫内膜样腺癌共计7例,低拷贝型、MSI-H型、POLE超突变型各有5例、1例、1例。40例患者分子分型p53状态、MMR蛋白表达、淋巴结转移、脉管浸润、FIGO分期、肿瘤病理类型、恶性肿瘤家族史比较,差异有统计学意义(P<0.05)。在3年随访期间未出现患者死亡事件,复发例数共计11例,复发率为22.50%,其中高拷贝型、低拷贝型、MSI-H型复发率各为55.56%、22.22%、22.22%。在无进展生存率分布情况中,高拷贝型为52.50%,低拷贝型为92.50%,MSI-H型为77.50%,POLE超突变型为100%。结论子宫内膜癌分子分型能够为病情预后与治疗提供参考依据,确保患者得到更有效的治疗,值得临床应用。

扬州市某医院早期自然流产胚胎染色体微阵列分析

目的探讨染色体微阵列分析(chromosomal microarray analysis,CMA)在早期自然流产中的病因学诊断价值,并研究流产物染色体异常与早期自然流产的关系。方法回顾性分析2017年6月至2022年12月在扬州市妇幼保健院确诊的432例患者的早期自然流产胚胎CMA结果,并分析不同胎停孕周与染色体数目异常和拷贝数异常之间的关联性。结果CMA成功检测428例,共有270例检出染色体异常,包括染色体数目异常212例,拷贝数异常53例和单亲二倍体5例。在染色体异常中染色体三体数目异常占比较大,其中又以16号染色体三体最为常见;拷贝数异常中检测出31例致病性和可能致病性拷贝数异常,22例临床意义不明的拷贝数异常。染色体数目异常在不同胎停孕周的差异无统计学意义(P>0.05),拷贝数异常检出率在孕10~11+6周时最高。结论CMA可明确早期自然流产的病因学诊断,其不仅可检测染色体数目异常,还可检出拷贝数异常甚至染色体微缺失综合征、染色体微重复综合征;本研究中引起自然流产最主要的原因是染色体数目异常。

人恶性胸膜间皮瘤DNA从头测序及基因突变分析

通过DNA从头测序分析人胸膜间皮瘤发生的高关联度突变基因。提取恶性胸膜间皮瘤(MPM)组织和正常胸膜组织DNA,构建基因文库,用Illumina HiSeqX Ten PE 150平台测序,将测序结果与人类基因组数据库的参考序列进行比对、注释,并对测序结果进行过滤、错误率分布检查、GC含量分布检查分析。MPM组织DNA平均过滤37829946 bp,错误率小于0.12%,GC含量占41.17%,而正常胸膜组织DNA平均过滤39089681 bp,错误率小于0.1%,GC含量占41.7%,两者测序质量均在Q 30(≥80%)以上,MPM为87.43%,正常胸膜为88.36%。以上高质量测序数据通过BWA比对到参考基因组(GRCh 37/hg 19),得到最初比对序列,利用重复标记后的比对序列进行覆盖度、深度等统计,覆盖深度达到10 X以上该突变位点可信。结果显示,实验病例XL14覆盖深度达到10 X的占98.59%,覆盖率达到99.83%;对照病例Z5占98.50%,覆盖率达到99.79%。对该序列进行基因注释分析,发现一系列单核苷酸多态性、基因插入缺失、基因结构变异、基因拷贝数变异,筛选出总变异位点数29277个,可能致病的变异位点数22个,致病性的变异位点数5个,不确定变异有害性的位点数为3353个,其余变异位点均为良性。进一步对突变基因进行富集、关联性分析,预测出突变基因TXNDC2与人胸膜间皮瘤的发生高度相关,相关系数达到0.8以上;突变基因PIEN、ABCC1、UGT1A7、UGT1A3、UGT1A4、UGT1A9、ALDH3B1、UGT1A5等与人胸膜间皮瘤有一定关联性,关联度在0~0.2之间。基因TXNDC2、PIEN、ABCC1、UGT1A7、UGT1A3、UGT1A4、UGT1A9、ALDH3B1、UGT1A5的变异可能与人胸膜间皮瘤的发生发展有关。本实验为人胸膜间皮瘤分子诊断提供了参考。