Novel Metrics for Mutation Analysis

A measure of the“goodness”or efficiency of the test suite is used to determine the proficiency of a test suite.The appropriateness of the test suite is determined through mutation analysis.Several Finite State Machine(FSM)mutants are produced in mutation analysis by injecting errors against hypotheses.These mutants serve as test subjects for the test suite(TS).The effectiveness of the test suite is proportional to the number of eliminated mutants.The most effective test suite is the one that removes the most significant number of mutants at the optimal time.It is difficult to determine the fault detection ratio of the system.Because it is difficult to identify the system’s potential flaws precisely.In mutation testing,the Fault Detection Ratio(FDR)metric is currently used to express the adequacy of a test suite.However,there are some issues with this metric.If both test suites have the same defect detection rate,the smaller of the two tests is preferred.The test case(TC)is affected by the same issue.The smaller two test cases with identical performance are assumed to have superior performance.Another difficulty involves time.The performance of numerous vehicles claiming to have a perfect mutant capture time is problematic.Our study developed three metrics to address these issues:FDR/|TS|,FDR/|TC|,and FDR/|Time|;In this context,most used test generation tools were examined and tested using the developed metrics.Thanks to the metrics we have developed,the research contributes to eliminating the problems related to performance measurement by integrating the missing parameters into the system.

Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia:A case report

BACKGROUND Hereditary spastic paraplegia(HSP)is a group of neurogenetic diseases of the corticospinal tract,accompanied by distinct spasticity and weakness of the lower extremities.Mutations in the spastic paraplegia type 4(SPG4)gene,encoding the spastin protein,are the major cause of the disease.This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene.CASE SUMMARY A 44-year-old male was admitted to our hospital for long-term right lower limb weakness,leg stiffness,and unstable walking.His symptoms gradually worsened,while no obvious muscle atrophy in the lower limbs was found.Neurological examinations revealed that the muscle strength of the lower limbs was normal,and knee reflex hyperreflexia and bilateral positive Babinski signs were detected.Members of his family also had the same symptoms.Using mutation analysis,a novel heterozygous duplication mutation,c.1053dupA,p.(Gln352Thrfs*15),was identified in the SPG4 gene in this family.CONCLUSION A Chinese family with HSP had a novel mutation of the SPG4 gene,which is autosomal dominant and inherited as pure HSP.The age of onset,sex distribution,and clinical manifestations of all existing living patients in this family were analyzed.The findings may extend the current knowledge on the existing mutations in the SPG4 gene.

Study on MCM Interconnect Test Generation Based on Ant Algorithm with Mutation Operator

A novel multi-chip module(MCM) interconnect test generation scheme based on ant algorithm(AA) with mutation operator was presented.By combing the characteristics of MCM interconnect test generation,the pheromone updating rule and state transition rule of AA is designed.Using mutation operator,this scheme overcomes ordinary AA’s defects of slow convergence speed,easy to get stagnate,and low ability of full search.The international standard MCM benchmark circuit provided by the MCNC group was used to verify the approach.The results of simulation experiments,which compare to the results of standard ant algorithm,genetic algorithm(GA) and other deterministic interconnecting algorithms,show that the proposed scheme can achieve high fault coverage,compact test set and short CPU time,that it is a newer optimized method deserving research.

Towards Semantic Mutation Testing of Aspect-Oriented Programs

Aspect-oriented programs have received much attention from software testing researchers. Various testing techniques and approaches have been proposed to tackle issues and challenges when testing aspect-oriented programs including traditional mutation testing. In traditional mutation testing of aspect-oriented programs, mutants are generated by making small changes to the syntax of the aspect-oriented language. Recently, a new approach known as semantic mutation testing has been proposed. This approach mutates the semantics of the language in which the program is written. The mutants generated misunderstandings of the language which are different classes of faults. Aspect-oriented programming presents itself with different properties that can be further explored with respect to semantic mutation testing. This paper describes various possible scenarios that semantic mutation testing strategy might have particular value in testing aspect-oriented programs.

ACE gene missense mutation in a case with early-onset, rapid progressing dementia

The population of early-onset Alzheimer's disease(EOAD)accounts for 1%-2%of the total population of Alzheimer's disease,and genetic mutations are more common in EOAD.The first symptom of the patient in the present case report was the decline in memories of recent events,and the disease progressed rapidly in the following 2 years.Genetic testing has revealed the presence of genetic mutations(c.A479G,p.N160S)of ACE,which causes the 160th codon of the ACE protein to change from aspartic acid to serine,and at the same time genotype of apolipoprotein E(APOE)is ε3/ε4.We think that this patient carries the mutation type of the sensitive gene ACE and the risk gene APOE of Alzheimer's disease,and this is the reason why the disease progressed rapidly.Moreover,we discussed ACE genetic mutation's meaning in EOAD progression.

Mutation Analysis of STR Locus on 23 Autosomes in Hainan Population

[Objective] To analyze the mutation signature and regularity of STR locus on 23 autosomes in paternity testing cases in Hainan. [Methods] A total of 2715 paternity testing cases accepted by the Forensic Medical Identification Centre of our hospital from 2017 to 2020 derived from counties and cities in Hainan Province were collected, the cases containing gene mutations were selected, the mutation rate and details of each locus were counted, and the mutation regu-larity of 23 STR loci was analyzed. [Results] Of the 2715 cases identified as “support”, 1487 were triplet cases and 1640 were dyad cases, totaling 4614 meioses;There were 50 gene mutation events (including 17 triplet mutations and 33 dyad mutations), with an average mutation rate of 0.0047% and a cumulative mutation rate of 1.0837%. A total of 19 of the 23 STR loci were mutated, with a mutation rate of 0.1301% at the D12S391 locus and 0.0217% at five loci, TPOX, D1S1656, D2S441, D22S1045, and PentaD, while no muta-tion events were found at four loci, D19S433, TH01, D13S317, and D7S820. Of the 50 mutation events, 47 were one-step mutations, 1 was two-step, and 2 were three-step. There were 35 paternal mutations (13 triplets and 22 dyads), 6 maternal mutations (4 triplets and 2 dyads), and 9 indeterminate pater-nal/maternal mutations, with a paternal to maternal mutation ratio of 5.83:1. [Conclusion] The mutation rate of D12S391 locus is the highest, and the muta-tion rate of TPOX, D1S1656, D2S441, D22S1045 and PentaD loci is the lowest in Hainan population, and paternal mutations are more than maternal muta-tions. In the paternity test, if 1 - 3 STR loci do not conform to the genetic law, especially when the mutant locus is homozygous or the next of kin is identi-fied, it is necessary to use other kits to review and increase the number of loci or use the second-generation sequencing technology to confirm, carefully de-termine the mutation and ensure the accuracy of the identification conclusion.

Establishment and application of a multiplex genetic mutation-detection method of lung cancer based on MassARRAY platform

Objective: This study aims to establish a method for highly parallel multiplexed detection of genetic mutations in Chinese lung cancer samples through Agena i PLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on Mass ARRAY mass spectrometry platform.Methods: We reviewed the related literature and data on lung cancer treatments. We also identified 99 mutation hot spots in 13 target genes closely related to the pathogenesis, drug resistance, and metastasis of lung cancer. A total of 297 primers, composed of99 paired forward and reverse amplification primers and 99 matched extension primers, were designed using Assay Design software. The detection method was established by analyzing eight cell lines and six lung cancer specimens. The proposed method was then validated through comparisons by using a Lung Carta^(TM) kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases.Results: The proposed method was able to detect multiplex genetic mutations in lung cancer cell lines. This finding was consistent with the observations on previously reported mutations. The proposed method can also detect such mutations in clinical lung cancer specimens. This result was consistent with the observations with Lung Carta^(TM) kit. However, an FGFR2 mutation was detected only through the proposed method. The measured sensitivity and specificity were 100% and 96.3%, respectively.Conclusions: The proposed Mass ARRAY technology-based multiplex method can detect genetic mutations in Chinese lung cancer patients. Therefore, the proposed method can be applied to detect mutations in other cancer tissues.

Relationship between Mutation of IR in the mtr System of Neisseria Gonorrhoeae and Multiple Antibiotic Resistance

To study the relationship between mutation of the inverted repeat sequence (IR) in the multiple transferable resistant system (mtr) of Neisseria gonorrhoeae (NG) and its multiple antibiotic resistance, minimal inhibitory concentrations (MICs) for the clinically isolated strains were tested by agar-dilution-method. The mtr system’s IR gene of NG was sequenced after amplification by polymerase chain reaction (PCR). Either two susceptive or five penicillin-resistant strains had no base mutation in IR gene, while all of the 13 strains with multiple-antibiotic-resistance had a single-base deletion (A/T). The result suggests that a single-base deletion of the thirteen-base IR sequence in mtr system of NG might result in multiple antibiotic resistance but is not associated with single antibiotic resistance.

A Novel Gene Mutation of Runx2 in Cleidocranial Dysplasia

Haploinsufficiency of the runt-related transcription factor 2(Runx2) gene is widely known to be responsible for cleidocranial dysplasia(CCD). To date, more than 190 mutations in Runx2 gene have been reported to be related to CCD. In this study, a novel mutation of Runx2 gene was observed in a female with CCD. Genomic DNA was extracted from peripheral venous blood of the proband and eleven members of her family. Genetic testing on these twelve people identified a novel missense mutation(c.895 T>C, Y299 H) in exon 5 of the RUNX2 gene in the proband. This mutation results in an amino acid change at codon 895(P.Tyr 299 His.) from a tryptophan codon(TAT) to a histidine codon(CAT). Our finding may further extend the known mutation spectrum of the RUNX2 gene, and facilitate prenatal genetic diagnosis of CCD in the future.

Implementation of Hybrid Particle Swarm Optimization for Optimized Regression Testing

Software test case optimization improves the efficiency of the software by proper structure and reduces the fault in the software.The existing research applies various optimization methods such as Genetic Algorithm,Crow Search Algorithm,Ant Colony Optimization,etc.,for test case optimization.The existing methods have limitations of lower efficiency in fault diagnosis,higher computa-tional time,and high memory requirement.The existing methods have lower effi-ciency in software test case optimization when the number of test cases is high.This research proposes the Tournament Winner Genetic Algorithm(TW-GA)method to improve the efficiency of software test case optimization.Hospital Information System(HIS)software was used to evaluate TW-GA model perfor-mance in test case optimization.The tournament Winner in the proposed method selects the instances with the best fitness values and increases the exploitation of the search to find the optimal solution.The TW-GA method has higher exploita-tion that helps to find the mutant and equivalent mutation that significantly increases fault diagnosis in the software.The TW-GA method discards the infor-mation with a lower fitness value that reduces the computational time and mem-ory requirement.The TW-GA method requires 5.47 s and the MOCSFO method requires 30 s for software test case optimization.

New real-time-PCR method to identify single point mutations in hepatitis C virus

AIM To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus(HCV).METHODS In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80 K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir. Low-cost, highly sensitive techniques enabling routine detection of these single point mutations would be useful to identify patients at a risk of treatment failure. Light Cycler methods, based on real-time PCR with sequencespecific probe hybridization, have been implemented in most diagnostic laboratories. However, this technique cannot identify single point mutations in highly variable genetic environments, such as the HCV genome. To circumvent this problem, we developed a new method to homogenize all nucleotides present in a region except the point mutation of interest. RESULTS Using nucleotide-specific probes Q, K, and R substitutions at position 80 were clearly identified at a sensitivity of 10%(mutations present at a frequency of at least 10% were detected). The technique was successfully applied to identify the Q80 K substitution in 240 HCV G1 serum samples, with performance comparable to that of direct Sanger sequencing, the current standard procedure for this purpose. The new method was then validated in a Catalonian population of 202 HCV G1-infected individuals. Q80 K was detected in 14.6% of G1 a patients and 0% of G1 b in our setting. CONCLUSION A fast, low-cost diagnostic strategy based on real-time PCR and fluorescence resonance energy transfer probe melting curve analysis has been successfully developed to identify single point mutations in highly variable genomes such as hepatitis C virus. This technique can be adapted to detect any single point mutation in highly variable genomes.

泰安市蒸发量变化趋势分析与基于神经网络的预测

蒸发量是水文特征里的一个重要指标,为科学准确地分析及预测泰安市蒸发量的特点和走势,利用泰安市黄前水库、东周水库、大汶口和戴村坝4个代表性水文观测站1985—2021年的调查数据,通过Mann-Kendall检验法、滑动t检验法检测其突变特征后,使用R/S分析法预测未来蒸发量变化趋势。使用泰安站2005—2022年蒸发量日值观测数据,通过Neural-Prophet算法耦合Optuna算法建模进行蒸发量的预测,并与其他预测模型的评价指标做出比较。结果表明:泰安市年及各季的蒸发量都呈现出明显的减少趋势,且在今后的一段时期内,大部分区域都将延续这样的发展态势。模型给出的预测数据准确率很高,符合要求,可以利用到日常生产及科研指导中,为蒸发量的预测提供了一种新途径。

测试集有效性评价:问题、进展与挑战

测试用例集的缺陷检测有效性指测试集能够在多大程度上检测出软件中存在的缺陷.如何评价测试集的缺陷检测有效性是一个重要问题.覆盖率和变异得分是两个最重要和最广泛使用的测试集有效性度量.为量化测试集的缺陷检测能力,研究人员对测试集有效性评价进行了大量研究并且取得了较大的进展.与此同时,现有研究存在不一致的结论,该领域依然存在一些亟待解决的挑战.对多年来国内外学者在测试集有效性评价领域的研究成果进行系统性的梳理和总结.首先,阐述测试集有效性评价研究中的问题.然后,介绍并分析基于覆盖率和基于变异得分的测试集有效性的评价以及介绍测试集有效性评价在测试集优化中的应用.最后,指出测试集有效性评价研究中面临的挑战并给出建议的研究方向.

儿童原发性扩张型心肌病的遗传因素及死亡危险因素研究

背景扩张型心肌病(DCM)是儿童心源性猝死和心力衰竭的常见原因之一,不同病因与DCM患儿的预后显著相关。其中原发性DCM的占比最高且预后相对较差,特别是与遗传因素相关的患儿预后更差。因此基于遗传背景下的死亡危险因素分析将有利于DCM患儿的精准预后评估及危险分层。目的探讨儿童原发性DCM的遗传病因占比、遗传学特征及死亡危险因素。方法回顾性纳入2018年7月—2022年12月在河北省儿童医院住院治疗并完成基因检测的42例原发性DCM患儿的临床资料,收集患儿的基因检测结果。出院后定期于河北省儿童医院心内科门诊随访。以患儿死亡时间或2022-12-31为随访终点,根据随访结局将患儿分为死亡组(9例)与存活组(33例)。采用Kaplan-Meier法绘制患儿的生存曲线,生存曲线比较采用Log-rank检验。采用多因素COX比例风险模型分析患儿死亡的危险因素。结果患儿中位首诊年龄12(7,96)个月,中位随访时间24(9,36)个月。死亡组患儿中位随访时间8(0,11)个月,存活组中位随访时间30(12,39)个月,差异有统计学意义(Z=-2.19,P<0.05)。死亡组患儿男性、心功能分级Ⅲ/Ⅳ级、基因突变阳性占比高于生存组,左心室短轴缩短率(LVFS)低于生存组(P<0.05)。患儿基因突变阳性率为38.1%(16/42),其中自发突变占25.0%(4/16),基因突变阴性为61.9%(26/42)。死亡组9例患儿均在诊断后1年内死亡。基因突变阳性患儿死亡8例(50.0%,8/16),基因突变阴性患儿死亡1例(3.8%,1/26),组间死亡率差异有统计学意义(P<0.05)。基因突变阴性死亡患儿CSRP3(c.190C>T)杂合变异,致病分类为临床意义未明。绘制患儿Kaplan-Meier生存曲线,Log-rank检验结果显示基因突变阴性患儿生存率高于基因突变阳性患儿(χ^(2)=18.1,P<0.001)。多因素COX比例风险模型分析结果显示基因突变[HR=23.91,95%CI=(1.80~317.21),P=0.016]、心功能分级Ⅲ/Ⅳ级[HR=11.29,95%CI(1.13~112.68),P=0.039]为DCM患儿死亡的危险因素。结论本研究38.1%的原发性DCM患儿与遗传病因相关,诊断后第1年内是DCM患儿死亡的高发期,基因突变阳性的患儿预后更差。存在致病基因突变、首诊心功能分级Ⅲ/Ⅳ级是患儿死亡的独立危险因素。

1956—2019年元谋干热河谷潜在蒸散发的变化及影响因素

为探究元谋干热河谷地区潜在蒸散发变化特征及其影响因子,通过应用彭曼蒙特斯模型、曼-肯德尔突变检验、气候倾向率和距平相关方法,分时段分析1956—2019年逐日气象要素值。结果表明:元谋干热河谷地区潜在蒸散发整体呈极显著下降的趋势,年度潜在蒸散发在1982年发生突变;各季潜在蒸散发变化明显,变化速率从大到小依次为3—5月、12月—次年2月、6—8月、9—11月;除1956—1982年12月—次年2月,1982—2019年9—11月、12月—次年2月潜在蒸散发有所增长外,剩下时段都呈减少趋势,1982年为各季的突变点。潜在蒸散发转折点为1982年;1982年前,年度潜在蒸散发距平占主导;1982年后,负距平占据主导,2008、2015年发生两次较大的波动。元谋干热河谷地区年潜在蒸散发变化主要取决于日照时间、气温和平均相对湿度;各季潜在蒸散发主要是由各气象要素共同作用的结果,且具有季节性差异;1982年以前,6—8月、9—11月潜在蒸散发的减少和12月—次年2月潜在蒸散发的增加仅与平均风速的减弱有关。

世界卫生组织《结核分枝杆菌耐药相关基因突变目录(第2版)》解读

耐药结核病是2035年实现全球终结结核病流行目标的巨大障碍。世界卫生组织(World Health Organization,WHO)倡导采用快速分子药物敏感性检测技术进行耐药结核病早期诊断,而覆盖全面可靠的耐药检测靶标是提高分子药物敏感性检测技术可靠性的关键。WHO于2023年11月发布《结核分枝杆菌耐药相关基因突变目录(第2版)》,目的是基于更广泛的全球数据汇总形成更为全面准确的耐药相关基因突变目录,为开发与完善基于测序或其他方法的新型分子药物敏感性检测技术提供支持。本文对第2版目录相较于第1版目录在分析流程与耐药突变等内容的更新进行了详细的解读,并对未来目录完善的方向进行了展望。

1960-2015年唐秦地区降雨及侵蚀性降雨变化趋势及突变分析

降雨是水力侵蚀的主因,降雨的地理分异规律是各地水力侵蚀特性差异的主因,因此研究降雨时间变化特征对区域水土保持工作具有重要意义。应用变化趋势和突变分析方法(Mann-Kendall检验)对唐秦地区1960—2015年降雨及侵蚀性降雨变化趋势及突变进行分析。结果表明:1)唐秦地区多年平均降雨量639.19 mm,呈波动下降趋势,平均每年减少1.46 mm;多年平均侵蚀性降雨量为443.78 mm,呈波动下降趋势,平均每年减少1.58 mm。2)季降雨特点为夏季降雨最多,平均降雨量466.15 mm,占全年降雨的72%,春秋2季次之,冬季最少;夏季降雨呈波动下降走势,气候倾向率为-3.0011/a,春、秋和冬季降雨呈波动上升走势,气候倾向率分别为0.5083/a、0.4586/a和0.2075/a。3)夏季侵蚀性降雨呈波动下降走势,气候倾向率为-2.2275/a,春季和秋季侵蚀性降雨量呈波动上升趋势,气候倾向率分别为0.1946/a和0.5361/a。4)年降雨突变发生在1996和2011年,年侵蚀性降雨量突变发生在2012年;季节变化上,春季降雨及侵蚀性降雨分别在1965和2013年发生突变,夏季降雨及侵蚀性降雨突变年份在1989和2012年,秋季降雨突变点为2003年,侵蚀性降雨突变年份为2006年,冬季突变年份在1984年。唐秦地区地形复杂,降雨变化规律多变,夏季降雨量多且侵蚀性降雨量大,需加强水土流失防治工作,同时该规律可为唐秦地区水土保持监测工作提供依据。

阿尔泰山河谷林径向生长对气候的响应

阿尔泰山林区是新疆十分重要的生态屏障,研究阿尔泰山树木的生长规律及其对气候的响应十分重要。基于树木年轮学为基础,选择布尔津、哈巴河和北屯3个采样点,采用相关性分析及Mann-Kendall突变检验探究阿尔泰山河谷林径向生长变化特征及其对气候变化的响应。结果表明:(1)布尔津树轮宽度年表平均敏感度、标准差、树间相关系数和第一特征向量百分比最大,说明该标准化年表包含的气候信息最丰富的,其次是北屯。(2)河谷林3个样点树轮宽度指数变化均呈上升趋势,且经Mann-Kendall突变检验,哈巴河、北屯样点树轮年表的突变时间均在年平均气温和年降水量突变时间之后,说明树轮生长有“滞后效应”。(3)哈巴河样点树轮宽度指数与前一年降水量呈显著正相关(P<0.01),北屯样点树轮宽度指数与当年降水量呈显著正相关(P<0.01),说明树轮宽度指数与降水相关性较强,与气温相关性较弱。(4)布尔津树轮年表受温度影响大,从生长季开始到生长季中后期,均与气温呈显著正相关,北屯树轮年表与降水呈显著正相关,与生长季末期的平均温度呈显著负相关。研究表明即使在相似生境下树木生长的影响因素也不同,布尔津样点树木受到开始生长时温度和结束时降水的影响较大,而北屯和哈巴河受生长季降水因素影响更为突出。

基于时序聚类及改进Pettitt的系统谐波阻抗估计

针对谐波电压与电流数据出现严重无序性,导致常规非干预式方法难以对系统谐波阻抗进行准确的实时估计,提出一种基于时序聚类及改进Pettitt的系统谐波阻抗估计方法。首先,运用时序聚类中互相关系数原理使谐波电压和电流序列平移对齐并筛选出强相关性的数据。然后,为了规避阻抗突变的影响,提出基于二元分割的Pettitt方法对阻抗突变点进行检验。最后,使用再生权最小二乘法,通过赋权重系数进一步减小异常值对结果的影响。仿真与实例结果表明,本文方法可以有效降低背景谐波波动和阻抗突变对系统谐波阻抗估计带来的误差。

Spatio-temporal Variation Characteristics of Extreme Climate Events and Their Teleconnections to Large-scale Ocean-atmospheric Circulation Patterns in Huaihe River Basin,China During 1959–2019

Huaihe River Basin(HRB) is located in China’s north-south climatic transition zone,which is very sensitive to global climate change.Based on the daily maximum temperature,minimum temperature,and precipitation data of 40 meteorological stations and nine monthly large-scale ocean-atmospheric circulation indices data during 1959–2019,we present an assessment of the spatial and temporal variations of extreme temperature and precipitation events in the HRB using nine extreme climate indices,and analyze the teleconnection relationship between extreme climate indices and large-scale ocean-atmospheric circulation indices.The results show that warm extreme indices show a significant(P < 0.05) increasing trend,while cold extreme indices(except for cold spell duration) and diurnal temperature range(DTR) show a significant decreasing trend.Furthermore,all extreme temperature indices show significant mutations during 1959-2019.Spatially,a stronger warming trend occurs in eastern HRB than western HRB,while maximum 5-d precipitation(Rx5day) and rainstorm days(R25) show an increasing trend in the southern,central,and northwestern regions of HRB.Arctic oscillation(AO),Atlantic multidecadal oscillation(AMO),and East Atlantic/Western Russia(EA/WR) have a stronger correlation with extreme climate indices compared to other circulation indices.AO and AMO(EA/WR) exhibit a significant(P < 0.05) negative(positive)correlation with frost days and diurnal temperature range.Extreme warm events are strongly correlated with the variability of AMO and EA/WR in most parts of HRB,while extreme cold events are closely related to the variability of AO and AMO in eastern HRB.In contrast,AMO,AO,and EA/WR show limited impacts on extreme precipitation events in most parts of HRB.