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The Highest Mutation in mtDNA Hypervariable Region and Application of Biostatistics with Nucleotide Base X t-n in Determining the Identity of the Mutation through a Transition Intensity Matrix mtDNA高变区最高突变及其应用核苷酸碱基X - t-n生物统计学通过过渡强度矩阵确定突变的身份
Pub Date : 2018-01-01 DOI: 10.4172/2153-0602.1000213
Palit Eiy, Y. Ngili
Human mitochondrial DNA (mtDNA) have been used intensively in the field of forensic identification of victims or suspects of crime through biological evidence. The number of mtDNA molecules in a single cell are in the tens of thousands which enable analysis of samples very little or damaged. Till now there is no standard method for identification using mtDNA in a mass disaster victims such as natural disasters, wars and accidents so that the identification process can not run fast. This study found C16.223t variants in mtDNA sequences that can be used to divide the database into two groups so as to accelerate the process of identification through a mathematical algorithm. This variant has the highest frequency (29.7%) of the 91 polymorphic human mtDNA HVS1 along the 300 nucleotide (16,024-16,324) derived from the NCBI database as much as 142 sequences. MtDNA sequences obtained from data collection Papuan human mtDNA groups that have been published in the NCBI. The next variant that can be used as a classifier in a row in the sequence is 16,311; 16,304; 16,189; and 16,270 with the identity (T→c). For a matrix Q is reversible so the matrix and could have the opposite diagonal. Thus the above equation can be solved by using the diagonal method that can be written: U³ = Uµ רUµ aµ†1 . This equation could count the number of transitions and transversion substitution mutations that occur in a nucleotide sequence of mtDNA. With this grouping, the database can be reduced so as to accelerate the process of identification of samples. Expected method of grouping by the variant with the highest frequency can be developed in the codification database for forensic interest such as the police or the mtDNA database purposes of study anthropology and evolutionary biology.
人类线粒体DNA (mtDNA)已被广泛应用于通过生物证据对被害人或犯罪嫌疑人进行法医鉴定。单个细胞中mtDNA分子的数量数以万计,这使得分析样品很少或损坏。目前,针对自然灾害、战争、事故等重大灾害受害者的mtDNA鉴定还没有统一的标准方法,导致鉴定过程无法快速进行。本研究在mtDNA序列中发现了C16.223t变异,可用于将数据库分为两组,从而通过数学算法加快鉴定过程。该变异在NCBI数据库中多达142个序列的300个核苷酸(16,024-16,324)沿线的91个多态人类mtDNA HVS1中频率最高(29.7%)。从已在NCBI上发表的巴布亚人MtDNA组数据收集中获得的MtDNA序列。下一个可以在序列的一行中用作分类器的变体是16,311;16304;16189;16270的恒等式为(T→c)。对于矩阵Q是可逆的所以矩阵和可以有相反的对角线。因此,上面的方程可以用对角线法求解,可以写成:U³= U μ רU μ a μ μ 1。这个方程可以计算mtDNA核苷酸序列中发生的转变和翻转取代突变的数量。通过这种分组,可以减少数据库,从而加快样本识别的过程。根据频率最高的变异进行分组的预期方法可以在法医学数据库(如警察)或mtDNA数据库(用于研究人类学和进化生物学)中开发。
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引用次数: 1
Vertebrate Arylsulfatase K (ARSK): Comparative and Evolutionary Studies of the Lysosomal 2-Sulfoglucuronate Sulfatase 脊椎动物芳基硫酸酯酶K (ARSK):溶酶体2-硫脲酸酯硫酸酯酶的比较和进化研究
Pub Date : 2018-01-01 DOI: 10.4172/2153-0602.1000212
R. Holmes
Arylsulfatase K (ARSK) is one of 17 sulfatase gene family members encoded on the human genome for which a role has been recently identified as a lysosomal 2-sulfoglucuronate sulfatase. Vertebrate ARSK sequences shared 60-82% identity but only <27% identities with other arylsulfatase family members. Comparative enzyme structures were studied, including residues with predicted roles in forming N-glycosylation sites, Ca2+ binding and active site residues. Vertebrate ARSK genes usually contained 8 coding exons. A human ARSK gene promoter comprised CpG61 and multiple TFBS, which may be involved in signal transduction, transcription activation or regulating entry into cell division. Phylogenetic analyses examined evolutionary changes for the vertebrate ARSK and the invertebrate SUL1 genes. In summary, a major role for this enzyme as a 2-sulfoglucuronate sulfatase is supported which has been conserved throughout vertebrate evolution.
Arylsulfatase K (ARSK)是人类基因组编码的17个硫酸盐酶基因家族成员之一,其作用最近被确定为溶酶体2-硫脲酸盐硫酸盐酶。脊椎动物ARSK序列与其他芳基磺化酶家族成员具有60-82%的同源性,但同源性仅<27%。研究了比较酶的结构,包括在形成n -糖基化位点、Ca2+结合位点和活性位点残基中具有预测作用的残基。脊椎动物的ARSK基因通常包含8个编码外显子。人类ARSK基因启动子由CpG61和多个TFBS组成,可能参与信号转导、转录激活或调节进入细胞分裂。系统发育分析检查了脊椎动物ARSK和无脊椎动物SUL1基因的进化变化。总之,该酶作为2-硫脲酸盐硫酸酯酶的主要作用在整个脊椎动物进化过程中得到了支持。
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引用次数: 0
Molecular Modeling and Simulation of Human Stomatin and Predictions for its Membrane Association 人类口蛋白的分子建模和模拟及其膜关联预测
Pub Date : 2018-01-01 DOI: 10.4172/2153-0602.1000216
Yosuke Kondo, H. Yokoyama, I. Matsui, S. Miyazaki
Stomatin is a membrane protein in human red blood cells. The crystal structure, in which the monomeric stomatin from the hyperthermophilic archaeon Pyrococcus horikoshii consists of the α/β domain and the C-terminal α-helical segment, forms a homo-trimer, and stomatin is organized into further high order homo-oligomeric complexes, comprising 9- to 12-mers. To better understand the molecular functions of stomatin, the hypothesis how human stomatin oligomerizes and is associated with cell membranes should be validated. Here, we report what conformations can be generated from the stomatin structure by estimating the flexibility of α-helical segments of human stomatin. And we also simulate how the oligomeric structure of human stomatin interacts with cell membranes. The results showed that the α-helical segments can make flexible movements; the α-helical segment and the α/β domain of the monomer can form a flat structure, and the α-helical segments of the trimer can approach lipid membranes. Based on the flat structure of human stomatin, we proposed a hypothetical oligomeric model to interact with the surface of cell membranes. The oligomeric model well explains the stomatin functions as a scaffolding protein to support the cell membrane.
口蛋白是人体红细胞中的一种膜蛋白。在晶体结构中,来自嗜热古细菌的单体口蛋白由α/β结构域和c端α-螺旋段组成,形成一个同源三聚体,口蛋白被组织成更高阶的同源低聚物,包括9- 12-mers。为了更好地理解口蛋白的分子功能,应该验证人类口蛋白如何寡聚并与细胞膜相关的假设。在这里,我们报告了通过估计人类口蛋白α-螺旋段的灵活性可以从口蛋白结构中产生什么构象。我们还模拟了人类口素的低聚结构是如何与细胞膜相互作用的。结果表明:α-螺旋节段具有柔性运动;单体的α-螺旋段和α/β结构域可形成扁平结构,三聚体的α-螺旋段可接近脂质膜。基于人类口蛋白的扁平结构,我们提出了一个假设的低聚体模型来与细胞膜表面相互作用。寡聚体模型很好地解释了气孔蛋白作为支撑细胞膜的支架蛋白的功能。
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引用次数: 3
Analysis and Mutation of Codon in rpoB and katG Genes and Bioinformatics Study of RIF Binding Model by RNA β Polymerase Subunit: Study in Tuberculosis Patients at Merauke General Hospital-Indonesia rpoB和katG基因密码子分析与突变及RNA β聚合酶亚基RIF结合模型的生物信息学研究——印度尼西亚Merauke总医院肺结核患者的研究
Pub Date : 2018-01-01 DOI: 10.4172/2153-0602.1000214
Kawulur Hsi, Y. Ngili
Treatment of TB patients is usually done by administering three types of antituberculosis drugs with the main options being Rifampin (RIF) and Isoniazid (INH), then accompanied by streptomycin or pyrazinamide. RIF resistance is attributable to the mutation of the rpoB gene, the gene that produces the RNA polymerase β-subunit, and the INH resistance is largely due to the mutation of the katG gene. The aim of this study was to obtain information on the association of MDR-TB with related genes, as well as information on the combination of Mycobacterium tuberculosis genotype in tuberculosis patients in Merauke. Here we reported that most of the MDRTB isolates are resistant to other antituberculosis drugs, and the mutation frequency of rpoB526 and rpoB531 (mutations that occur on both sides/this place almost always occur together) is almost the same but the katG315 mutation is present in only 16 isolates (the number of mutations that occur in katG315 is less than in rpoB526 and rpoB531). The presence of C1363A nucleotide changes in sensitive Mycobacterium tuberculosis of six antituberculosis drugs showed that not all rpoB mutations caused resistance. On the basis of this phenomenon, it can be proposed that the mechanism of formation of MDR-TB strains begins with a rpoB mutation followed by a mutation of katG. This study demonstrates that the mechanism of resistance to a drug that affects only one gene, such as rifampin that affects rpoB, is more easily controlled than antituberculous drugs affecting several genes, such as isoniazid which affects other genes besides katG.
结核病患者的治疗通常通过使用三种类型的抗结核药物来完成,主要选择是利福平(RIF)和异烟肼(INH),然后伴随着链霉素或吡嗪酰胺。RIF耐药主要是由于产生RNA聚合酶β-亚基的基因rpoB基因突变,INH耐药主要是由于katG基因突变。本研究的目的是获得耐多药结核病与相关基因的关联信息,以及Merauke结核病患者中结核分枝杆菌基因型组合的信息。本研究发现,大多数MDRTB分离株对其他抗结核药物具有耐药性,rpoB526和rpoB531的突变频率(突变发生在两侧/几乎总是同时发生)几乎相同,但katG315突变仅在16株分离株中存在(katG315突变的数量少于rpoB526和rpoB531)。在6种抗结核药物的敏感结核分枝杆菌中存在C1363A核苷酸变化,表明并非所有rpoB突变都引起耐药性。基于这一现象,可以提出MDR-TB菌株的形成机制始于rpoB突变,随后是katG突变。本研究表明,对仅影响一个基因的药物(如影响rpoB的利福平)的耐药机制比影响多个基因的抗结核药物(如影响katG以外其他基因的异烟肼)更容易控制。
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引用次数: 1
Mitochondrial Genome Mutation Analysis: Indonesian Human mtG Comparation and Several GenBank Sequence Data on Gene Control and Encoding Regions 线粒体基因组突变分析:印度尼西亚人mtG比较和基因控制和编码区域的几个GenBank序列数据
Pub Date : 2018-01-01 DOI: 10.4172/2153-0602.1000215
Y. Ngili, J. Siallagan, Tanjung Rhr, Palit Eiy
Comparative study of DNA mutations occurring in human mitochondrial genomes in Indonesian humans and its comparison with some ethnic worlds has been done. The purpose of this study was to analyze mutant variants in all the complete human genome mitochondrial areas by using G-repliant techniques for mitochondrial genomic amplification, the result of Indonesian human nucleotide sequencing was then compared against some individuals representing some ethnicities in the world. DNA samples were isolated from human tissue and then sequenced using 10 pairs of primers to amplify human mtG. The mtG sequence is aligned and compared with rCRS using the DNAstar program. The result of mutation analysis shows the presence of point mutation in some mtG region fragments with different mutation proportions. Most mutations outside the HVS1 and HVS2 D-loops are in the ATP6 region. The encoding region of ATP6 is the gene coding region of human mtG and shows a high mutation rate of CRS. This opens a new paradigm for mutation analysis on ATP6 areas other than the mtG D-loop. The ATP6 gene segment located at 8553-8902 can be selected for studies in population genetics, forensic medicine and bioethnoanthropology studies, in addition to the HVS1/HVS2 D-loop areas that have been used.
对印度尼西亚人线粒体基因组发生的DNA突变进行了比较研究,并与一些民族进行了比较。本研究的目的是利用g -复制技术进行线粒体基因组扩增,分析人类基因组所有线粒体区域的突变变异,并将印度尼西亚人核苷酸测序结果与世界上一些种族的一些个体进行比较。从人组织中分离DNA样本,用10对引物扩增人mtG序列,用DNAstar程序比对mtG序列并与rCRS进行比较。突变分析结果表明,不同突变比例的mtG区片段存在点突变。大多数HVS1和HVS2 d -环外的突变都在ATP6区。ATP6的编码区是人类mtG的基因编码区,CRS的突变率较高。这为mtG D-loop以外的ATP6区域的突变分析开辟了新的范式。位于8553-8902的ATP6基因片段除了已经使用的HVS1/HVS2 D-loop区域外,还可用于群体遗传学、法医学和生物民族人类学研究。
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引用次数: 0
Organellar Proteomics: Tissue Specificity, Absolute Quantity, PosttranslationalModifications and Protein-Protein Interactions 器官蛋白质组学:组织特异性,绝对数量,翻译后修饰和蛋白质-蛋白质相互作用
Pub Date : 2017-03-24 DOI: 10.4172/2153-0602.1000E129
Moussa Ae, X. Chen
Organellar proteomics combines subcellular fractionation and mass spectrometry-based protein identifications. In the past decades, organellar proteomic analysis has been carried out for virtually every subcellular compartment in mammalian cells and tissues [1-4]. While conventional biochemical and biophysical approaches study the structures and functions of individual proteins, mass spectrometrybased proteomic studies allow us to understand the entire proteome or sub proteome systematically by: (i) Identifying proteins present in each subcellular organelle; (ii) Quantifying their expression levels; and (iii) Characterizing their posttranslational modifications and proteinprotein interactions. All of the above determines the protein’s function and activity.
细胞质蛋白质组学结合亚细胞分离和质谱为基础的蛋白质鉴定。在过去的几十年里,对哺乳动物细胞和组织中几乎每一个亚细胞区室都进行了细胞器蛋白质组学分析[1-4]。传统的生物化学和生物物理方法研究单个蛋白质的结构和功能,而基于质谱的蛋白质组学研究使我们能够通过以下方式系统地了解整个蛋白质组或亚蛋白质组:(i)识别存在于每个亚细胞细胞器中的蛋白质;量化它们的表达水平;(iii)描述它们的翻译后修饰和蛋白-蛋白相互作用。所有这些决定了蛋白质的功能和活性。
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引用次数: 0
Insights into Genomic Variation within Salmonella enterica 肠道沙门氏菌基因组变异研究
Pub Date : 2017-03-23 DOI: 10.4172/2153-0602.1000E128
Serrano Pc, P. Lam, Hern, ez Ye, Nava Gm
Advances in molecular microbiology, comparative genomics and data mining have allowed us to uncover new insights into genome structure within bacterial species. To evolve, Bacteria gains and loses genes and other genomic sequences to adapt to specific ecological niches [1]. Thus, the intraspecies genomic variation found in numerous bacterial species has highlighted the need of analyzing genome composition to define bacterial species [1]. Fortunately, Whole-Genome Sequence Analysis (WGSA) has uncovered the dynamic nature of genomic plasticity and the consequent extensive genetic diversity in Bacteria [2]. Currently, microbiological research has been focused on WGSA within-species to identify molecular or virulence determinants. These studies could accelerate our understanding of bacterial pathogenesis and strains-specific traits of virulence; key factors in improving bacterial surveillance and development of antibacterial treatments or vaccines [3]. Herein, we investigate the genomic variation within Salmonella enterica as an example of the potential of comparative analysis of WGSA to uncover intraspecies variation. A total of 1,604 S. enterica whole genomes were analyzed. This dataset comprised 38 different serotypes (Table 1) retrieved from the Integrated Microbial Genomes (IMG) system [4]. Serotypes with at least 3 genomes available were used for bioinformatics analyses. Intraspecies traits of genomic variation were assessed for each of the selected serotypes. Briefly, it was found that the genome size S. enterica serotypes varies considerably; for example, serotype Muenchen, in average, possess the largest genome size (5.00 Mbp) whereas Paratyphi possess the smallest (4.59 Mbp). Unexpectedly, a high variation in the genome size was observed in each serotype (Figure 1 and Table 1).
分子微生物学、比较基因组学和数据挖掘的进步使我们能够发现细菌物种基因组结构的新见解。为了进化,细菌获得和失去基因和其他基因组序列,以适应特定的生态位[1]。因此,在许多细菌物种中发现的种内基因组变异突出了分析基因组组成来定义细菌物种的必要性[1]。幸运的是,全基因组序列分析(Whole-Genome Sequence Analysis, WGSA)揭示了细菌基因组可塑性的动态本质以及由此产生的广泛的遗传多样性[2]。目前,微生物学研究主要集中在物种内的WGSA,以确定分子或毒力决定因素。这些研究可以加速我们对细菌致病机制和菌株特异性毒力特征的理解;提高细菌监测和开发抗菌治疗或疫苗的关键因素[3]。在这里,我们研究肠道沙门氏菌的基因组变异,作为WGSA比较分析揭示种内变异的潜力的一个例子。共分析了1604份肠球菌全基因组。该数据集包括从集成微生物基因组(IMG)系统中检索的38种不同血清型(表1)[4]。至少有3个基因组可用的血清型用于生物信息学分析。对所选血清型的种内基因组变异特征进行了评估。简要地说,发现肠链球菌血清型的基因组大小差异很大;例如,平均而言,Muenchen血清型具有最大的基因组大小(5.00 Mbp),而副伤寒具有最小的基因组大小(4.59 Mbp)。出乎意料的是,在每种血清型中观察到基因组大小的高度变化(图1和表1)。
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引用次数: 0
Concerted Evolution of the Replication-Dependent Histone Gene Family in Drosophila immigrans 移民果蝇复制依赖组蛋白基因家族的协同进化
Pub Date : 2017-01-05 DOI: 10.4172/2153-0602.1000210
N. Kakubayashi
The replication-dependent histone genes in Drosophila immigrans were analyzed for elucidating the evolutionary mechanism of the histone multigene family. A region of approximately 3.9 kb containing H2A-H2B-H1 genes was cloned. Six independent clones were sequenced and analyzed for nucleotide variability. The average nucleotide sequence identity in the region among repetitive copies was more than 99%, indicating that the histone multigene family in D. immigrans has evolved in a concerted fashion and with a similar level as in D. melanogaster. Amino acid variants were found at a low frequency. Analysis of the GC content at the 3rd codon position of histone genes revealed that a change in GC content, i.e., a decrease, observed in D. hydei and D. americana has occurred after the divergence of an ancestor of these two species from D. immigrans.
为阐明组蛋白多基因家族的进化机制,对迁徙果蝇复制依赖性组蛋白基因进行了分析。克隆了一个含有H2A-H2B-H1基因的约3.9 kb区域。对6个独立克隆进行测序并分析核苷酸变异性。在重复拷贝中,该区域的平均核苷酸序列同源性超过99%,表明移民D.的组蛋白多基因家族以协调一致的方式进化,其水平与黑腹D.相似。氨基酸变异的发现频率较低。对组蛋白基因第3密码子位置GC含量的分析表明,在d.h dei和d.a americana中观察到的GC含量的变化,即减少,发生在这两个物种的祖先与d.a migrans分化之后。
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引用次数: 1
Obesity and Female Fertility: The Bridging Role of Leptin 肥胖和女性生育能力:瘦素的桥梁作用
Pub Date : 2017-01-01 DOI: 10.4172/2153-0602.1000209
P. Karoutsos
Leptin secretion is a requirement in order for both of energy balance and reproductive capacity to be preserved. That is because leptin plays an important role in appetite regulation and balance of body weight. Leptin binds to leptin receptor in the cells of the hypothalamus. This stimulates an intracrine signalling pathway that drives downregulation of the receptors expression involved in appetite increase. It is clearly set that leptin impairs production of sex steroid hormones in granulosa cells. In addition, alterations noted in follicular fluid from obese women include increased androgen activity and decreased human chorionic gonadotropin levels by other studies. Likewise, adiponectin levels are inversely correlated with levels of insulin, which by inhibiting the production of hepatic sex hormone binding globulin, because increased levels of androgens. On meeting with the fertility problems that arise among these women, scientists must understand the pathophysiology of adipose signalling on reproductive function.
瘦素的分泌是维持能量平衡和生殖能力所必需的。这是因为瘦素在食欲调节和体重平衡中起着重要作用。瘦素与下丘脑细胞中的瘦素受体结合。这刺激了分泌内信号通路,导致与食欲增加有关的受体表达下调。很明显,瘦素损害颗粒细胞中性类固醇激素的产生。此外,肥胖妇女卵泡液的改变还包括雄激素活性增加和绒毛膜促性腺激素水平降低。同样,脂联素水平与胰岛素水平呈负相关,胰岛素通过抑制肝脏性激素结合球蛋白的产生,因为雄激素水平升高。在遇到这些女性中出现的生育问题时,科学家必须了解脂肪信号对生殖功能的病理生理学。
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引用次数: 2
Epigenetics Evolution and Replacement Histones: Evolutionary Changesat Drosophila H2AvD 表观遗传学、进化和替代组蛋白:果蝇H2AvD的进化变化
Pub Date : 2017-01-01 DOI: 10.4172/2153-0602.1000207
Y. Matsuo
The evolutionary changes in the Drosophila H2A and H2AvD genes, which encode histones, were analyzed using the sequences of 12 Drosophila sp. for understanding the evolution of histone replacement and epigenetics. The Ball gene, coding for a histone threonine kinase, was located head-to-head with the H2AvD gene in seven Drosophila sp. A strongly conserved DNA sequence was also found in the region upstream of the H2AvD gene; this sequence is most likely a transcriptional signal, because the sequence was also conserved in four other Drosophila sp. that did not have an upstream Ball gene. The SPARC gene, coding for a calcium-binding domain, was located tail-to-tail in the region downstream of the H2AvD gene in 11 Drosophila sp. studied. A moderately conserved DNA sequence was found in the H2AvD gene region at the splicing site in the first intron. Different codon usages for the H2A and H2AvD genes were found for 11 of 17 amino acids, and codon usages characteristic of replacement histones (H2AvD, H4r, H3.3A and H3.3B) were found for amino acids. Codon usage was considerably different at several histone modification sites in the H2A gene. These results suggested that unlike the H3.3 and H4r genes, not only post-transcriptional control, but also transcriptional control played a role in the H2AvD gene. In addition to post-transcriptional controls, such as splicing and translation, the development of a control system for transcription must have occurred during the evolution of histone replacement and epigenetic systems.
利用12只果蝇的组蛋白编码基因H2A和H2AvD的序列,分析了组蛋白替代和表观遗传学的进化变化。在7只果蝇中,编码组蛋白苏氨酸激酶的Ball基因与H2AvD基因头部相连,在H2AvD基因上游区域也发现了一个高度保守的DNA序列;这个序列很可能是一个转录信号,因为这个序列在另外四个没有上游球基因的果蝇中也是保守的。在研究的11只果蝇中,编码钙结合域的SPARC基因位于H2AvD基因下游区域的尾尾相连。在第一个内含子剪接位点的H2AvD基因区域发现了一个中等保守的DNA序列。在17个氨基酸中,有11个发现H2A和H2AvD基因的密码子用法不同,氨基酸的密码子用法具有替代组蛋白(H2AvD、H4r、H3.3A和H3.3B)的特征。在H2A基因的几个组蛋白修饰位点上,密码子的使用有很大的不同。这些结果表明,与H3.3和H4r基因不同,H2AvD基因不仅发挥转录后调控的作用,还发挥转录调控的作用。除了剪接和翻译等转录后控制外,转录控制系统的发展一定发生在组蛋白替代和表观遗传系统的进化过程中。
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引用次数: 4
期刊
Journal of Data Mining in Genomics & Proteomics
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