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Boquila: NGS read simulator to eliminate read nucleotide bias in sequence analysis Boquila: NGS读取模拟器,以消除序列分析中读取的核苷酸偏差
IF 2.2 4区 生物学 Q3 BIOLOGY Pub Date : 2022-03-30 DOI: 10.1101/2022.03.29.486262
Umit Akkose, Ogun Adebali
Sequence content is heterogeneous throughout genomes. Therefore, Genome-wide NGS reads biased towards specific nucleotide profiles are affected by the genome-wide heterogeneous nucleotide distribution. Boquila generates sequences that mimic the nucleotide profile of true reads, which can be used to correct the nucleotide-based bias of genome-wide distribution of NGS reads. Boquila can be configured to generate reads from only specified regions of the reference genome. It also allows the use of input DNA sequencing to correct the bias due to the copy number variations in the genome. Boquila uses standard file formats for input and output data, and it can be easily integrated into any workflow for high-throughput sequencing applications.
序列内容在整个基因组中是异质的。因此,偏向于特定核苷酸谱的全基因组NGS读数受到全基因组异质核苷酸分布的影响。Boquila生成了模拟真实reads的核苷酸谱的序列,这可以用来纠正NGS reads全基因组分布中基于核苷酸的偏差。Boquila可以配置为仅从参考基因组的特定区域生成读取。它还允许使用输入DNA测序来纠正由于基因组拷贝数变化而产生的偏差。Boquila使用标准文件格式的输入和输出数据,它可以很容易地集成到任何工作流程的高通量测序应用程序。
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引用次数: 1
Developing a label propagation approach for cancer subtype identification problem 针对癌症亚型识别问题的标签传播方法研究
IF 2.2 4区 生物学 Q3 BIOLOGY Pub Date : 2022-01-01 DOI: 10.55730/1300-0152.2582
Pınar Güner, B. Güngör, Mustafa Coşkun
The term of cancer is used to describe diseases in which abnormal cells that grow out of control and invade other tissues. There are multiple types of cancer and many types of cancer have various subtypes with different clinical and biological implications. These differences show that diverse methods should be followed for the treatment of different subtypes of cancer. Discovering cancer subtypes is an important problem in bioinformatics, as it can help improve personalized medicine. Knowing the subtype of cancer is useful for determine the treatment steps and prognosis. Computational bioinformatics methods help performing cancer analysis to design targeted treatments by exposing the common molecular pathology of different cancer subtypes. Thus far, several computational methods have been proposed to discover cancer subtypes or to stratify cancer into informative subtypes. However, existing works do not consider the sparseness of data, and result in ill-conditioned solution. To resort this shortcoming, in this thesis, we propose an alternative unsupervised computational method to stratify cancer into subtypes using applied numerical algebra techniques. More specifically, we applied this label propagation-based approach to stratify somatic mutation profiles of colon, head and neck, uterine, bladder and breast tumors. We then evaluated the performance of our method by comparing it to the baseline methods. Extensive experiments demonstrate that our approach highly renders tumor classification tasks by largely outperforming the state-of-the-art unsupervised and supervised approaches. tiplerinin
癌症这个术语是用来描述异常细胞生长失控并侵入其他组织的疾病。有多种类型的癌症,许多类型的癌症有不同的亚型,具有不同的临床和生物学意义。这些差异表明,治疗不同亚型的癌症应采用不同的方法。发现癌症亚型是生物信息学中的一个重要问题,因为它可以帮助改善个性化医疗。了解癌症的亚型有助于确定治疗步骤和预后。计算生物信息学方法通过揭示不同癌症亚型的共同分子病理学,帮助进行癌症分析,设计靶向治疗。到目前为止,已经提出了几种计算方法来发现癌症亚型或将癌症分层为信息亚型。然而,现有的工作没有考虑数据的稀疏性,导致了病态解。为了弥补这一缺点,在本文中,我们提出了一种替代的无监督计算方法,使用应用数值代数技术将癌症分层为亚型。更具体地说,我们应用这种基于标签传播的方法对结肠、头颈部、子宫、膀胱和乳房肿瘤的体细胞突变谱进行分层。然后,我们通过将我们的方法与基线方法进行比较来评估我们的方法的性能。大量的实验表明,我们的方法在很大程度上优于最先进的无监督和有监督方法,从而高度呈现肿瘤分类任务。tiplerinin
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引用次数: 0
Prenatal exposure of diclofenac sodium alters the behavioral development of young Wistar rats 产前接触双氯芬酸钠对幼龄Wistar大鼠行为发育的影响
IF 2.2 4区 生物学 Q3 BIOLOGY Pub Date : 2019-10-14 DOI: 10.3906/biy-1904-33
B. Elibol, Begüm ARITAN OĞUR, H. Doğru
Diclofenac sodium (DS), a potent inhibitor of cyclooxygenase, reduces the release of arachidonic acid and formation of prostaglandins. Being a nonsteroid drug that shows antiinflammatory action, the possible side effects of fetal DS administration gain importance in public and medical applications. Herein, the effects of DS administration (1 mg/kg) during gestational days 5–20 were investigated on the performance of Wistar rat pups in a variety of behavioral tasks. Four-week-old pups were subjected to sensory motor tests, a plus maze, an open field, the Morris water maze, and a radial arm maze. Fetal DS disrupted some sensory motor performances, such as visual placing and climbing in both females and males. In the open field, DS females had a higher level of anxiety and male DS pups habituated to the environment slowly compared to controls. The DS pups showed slower rates of learning, whereas no substantial between-group differences were found in the performance of spatial memory compared to both controls. Furthermore, working memory was negatively affected by fetal DS. In conclusion, it was indicated that DS administration during pregnancy had slight behavioral impacts with a delay in learning and a defect in the short-term memory in juvenile rats.
双氯芬酸钠(DS)是一种有效的环氧合酶抑制剂,可减少花生四烯酸的释放和前列腺素的形成。作为一种具有抗炎作用的非甾体药物,胎儿DS给药可能产生的副作用在公共和医学应用中越来越重要。在此,研究了妊娠第5-20天DS给药(1 mg/kg)对Wistar大鼠幼崽在各种行为任务中表现的影响。四周大的幼崽接受了感觉运动测试、加号迷宫、开阔地、莫里斯水迷宫和桡臂迷宫。胎儿DS破坏了一些感觉运动表现,如女性和男性的视觉定位和攀爬。在开阔地里,与对照组相比,雌性DS幼崽的焦虑程度更高,雄性DS幼崽对环境的适应速度较慢。DS幼崽的学习速度较慢,而与两个对照组相比,在空间记忆表现方面没有发现显著的组间差异。此外,工作记忆受到胎儿DS的负面影响。总之,研究表明,妊娠期服用DS对幼年大鼠的行为影响很小,学习延迟,短期记忆有缺陷。
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引用次数: 1
Knockdown of SET Domain, Bifurcated 1 suppresses head and neck cancer cell viability and wound-healing ability in vitro 敲除SET结构域,分叉1抑制头部和颈部癌症细胞的生存能力和伤口愈合能力
IF 2.2 4区 生物学 Q3 BIOLOGY Pub Date : 2019-10-14 DOI: 10.3906/biy-1903-71
S. Özdaş
Head and neck cancer (HNC) is the sixth most common cancer worldwide and therefore presents a global public health problem. There are no standard algorithms for the diagnosis and follow-up of the disease, and no effective current treatment approaches exist. Therefore, the discovery of new biomolecules and the design of new strategies to aid in early diagnosis is necessary, along with establishing prognostic factors of HNC. In several cancer studies, the upregulation of SET Domain, Bifurcated 1 (SETDB1) has been reported to be tumor-inducing and to indicate a cancer-invasive prognosis, leading to the modulation of genes associated with different signaling pathways; however, the literature is sparse regarding the relationship between SETDB1 and HNC. In our study, three HNC primary cell lines and their corresponding metastatic cell lines were used. The quantitative reverse transcriptase-polymerase chain reaction and western blotting data indicated that the SETDB1 mRNA and protein expression levels were higher in all metastatic cell lines compared to their primary cell lines (P < 0.05 for all). To investigate the role of SETDB1 in HNC biology, in vitro functional analyses were carried out using small interference RNA (siRNA) technology, cell viability, scratch wound-healing, and the caspase-3 activity assay of gene expression of SETDB1 to compare primary and metastatic cell lines of HNC. Metastatic cells were more susceptible to this suppression, which decreased the vitality of cells and their ability of wound-healing and induced level of caspase-3 activity (P < 0.05 for all). This functional study has shown that SETDB1 plays an important role in head and neck carcinogenesis. Therefore, SETDB1 may be an attractive therapeutic target molecule and also a potential diagnostic and prognostic biomarker in HNC.
癌症是世界上第六大最常见的癌症,因此也是一个全球性的公共卫生问题。该疾病的诊断和随访没有标准的算法,目前也没有有效的治疗方法。因此,有必要发现新的生物分子并设计新的策略来帮助早期诊断,同时确定HNC的预后因素。在几项癌症研究中,SET结构域,分叉1(SETDB1)的上调已被报道为肿瘤诱导,并表明癌症的侵袭性预后,导致与不同信号通路相关的基因的调节;然而,关于SETDB1和HNC之间的关系的文献很少。在我们的研究中,使用了三种HNC原代细胞系及其相应的转移细胞系。定量逆转录聚合酶链式反应和蛋白质印迹数据表明,与原代细胞系相比,所有转移细胞系中SETDB1mRNA和蛋白质的表达水平均较高(所有细胞均P<0.05)。为了研究SETDB1在HNC生物学中的作用,使用小干扰RNA(siRNA)技术、细胞活力、划痕愈合和SETDB1基因表达的胱天蛋白酶-3活性测定进行了体外功能分析,以比较HNC的原代和转移细胞系。转移细胞更容易受到这种抑制,这降低了细胞的活力和伤口愈合能力,并诱导了胱天蛋白酶-3活性水平(均P<0.05)。这项功能研究表明SETDB1在头颈部癌变中起着重要作用。因此,SETDB1可能是一种有吸引力的治疗靶分子,也是HNC的潜在诊断和预后生物标志物。
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引用次数: 5
E2F6 is essential for cell viability in breast cancer cells during replication stress E2F6在复制应激期间对癌症乳腺细胞的细胞活力至关重要
IF 2.2 4区 生物学 Q3 BIOLOGY Pub Date : 2019-10-14 DOI: 10.3906/biy-1905-6
I. J. Lafta
E2F6 is a member of the E2F family of transcription factors involved in regulation of a wide variety of genes through both activation and repression. E2F6 has been reported as overexpressed in breast cancers but whether or not this is important for tumor development is unclear. We first checked E2F6 expression in tumor cDNAs and the protein level in a range of breast cancer cell lines. RNA interference-mediated depletion was then used to assess the importance of E2F6 expression in cell lines with regard to cell cycle profile using fluorescence-activated cell sorting and a cell survival assay using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The overexpression of E2F6 was confirmed in breast tumor cDNA samples and breast cancer cell lines. Depletion of E2F6 in the breast cancer cells reduced cell viability in MCF-7, T-47D, and MDA-MB-231 cells. There was little effect in the nontumor breast cell line MCF-10A. The deleterious effect on cancer cells was greater during replication stress, leading to an increase in the proportion of breast cancer cells with sub-G1 DNA content. These results suggest that E2F6 might be essential for the survival of breast cancer cells experiencing replication stress, and therefore it could be a target for combined therapy.
E2F6是转录因子E2F家族的成员,通过激活和抑制参与多种基因的调节。据报道,E2F6在乳腺癌中过表达,但这对肿瘤发展是否重要尚不清楚。我们首先检测了E2F6在肿瘤cDNA中的表达和一系列癌症细胞系中的蛋白质水平。然后,使用荧光激活的细胞分选和使用(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT)的细胞存活测定,使用RNA干扰介导的耗竭来评估细胞系中E2F6表达对细胞周期图的重要性。在乳腺肿瘤cDNA样品和乳腺癌症细胞系中证实了E2F6的过度表达。乳腺癌症细胞中E2F6的缺失降低了MCF-7、T-47D和MDA-MB-231细胞中的细胞活力。在非肿瘤乳腺细胞系MCF-10A中几乎没有作用。在复制应激期间,对癌症细胞的有害影响更大,导致具有亚G1 DNA含量的癌症乳腺细胞比例增加。这些结果表明,E2F6可能对经历复制应激的癌症细胞的生存至关重要,因此它可能是联合治疗的靶点。
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引用次数: 9
Cytotoxic and genotoxic action of Tagetes patula flower methanol extract and patuletin using the Allium test 用葱试验研究万寿菊花甲醇提取物和球曲素的细胞毒和基因毒作用
IF 2.2 4区 生物学 Q3 BIOLOGY Pub Date : 2019-10-14 DOI: 10.3906/biy-1906-7
M. Azhar, A. Farooq, S. Haque, S. Bano, Lubna Zaheer, S. Faizi
Tagetes patula is used to treat cancer patients in alternative healthcare systems. However, its cytotoxic and genotoxic effects have not been reported. Therefore, themethanol extract of T. patula flower, the ethyl acetate fraction, and the pure compound patuletin were evaluatedusing the Allium test.The methanol extract and fraction contained ~3% and ~36% patuletin, respectively, with ~98% purity. The methanol extract caused inhibition of Allium root growth displaying an IC50 value of ~500 µg/mL, while the fraction and patuletin were more potent by ~2 and ~5 times, respectively. The Allium root tips demonstrated a decline in prophase, metaphase, anaphase, and telophase stages with concomitant decrease in percent mitotic index in the methanol extract (~5.64), fraction, and patuletin (~4) as compared to the control (~7.61). However, in only methanol extract-treated root tips, an increase in metaphase stage was noted. In addition, the methanol extract predominantly induced c-type, misaligned, and multipolar chromosomal abnormalities while the fraction and patuletin displayed fragments and sticky chromosomes. The fraction and patuletin also produced micronuclei (~2%). In conclusion, T. patula flower methanol extract and ethyl acetate fraction are cytotoxicand genotoxic, which most likely could be due to the patuletin. Further preclinical and clinical studies are required to justify its clinical use.
万寿菊在替代医疗系统中用于治疗癌症患者。然而,其细胞毒性和基因毒性作用尚未见报道。因此,采用葱试验方法,对鸢尾花甲醇提取物、乙酸乙酯部分和复方鸢尾素纯品进行了评价。甲醇提取物和馏分中展曲素含量分别为~3%和~36%,纯度为~98%。甲醇提取物对葱根生长的抑制作用IC50值为~500µg/mL,而甲醇提取物和展曲素对葱根生长的抑制作用分别为~2和~5倍。与对照(~7.61)相比,甲醇提取物(~5.64)、馏分(~4)和展曲素(~7.61)使葱根尖的前期、中期、后期和末期均呈下降趋势,有丝分裂百分数也随之下降。然而,在只有甲醇提取物处理的根尖,中期阶段的增加被注意到。此外,甲醇提取物主要诱导c型、错位和多极染色体异常,而组分和展列素则显示片段和粘性染色体。该馏分和展列素也产生微核(~2%)。综上所述,鸢尾花甲醇提取物和乙酸乙酯部分具有细胞毒性和遗传毒性,很可能是由鸢尾花中的展列素引起的。需要进一步的临床前和临床研究来证明其临床应用的合理性。
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引用次数: 3
A new Helicoverpa armigera Nucleopolyhedrovirus isolate from Heliothis peltigera (Denis & Schiffermuller) (Lepidoptera: Noctuidae) in Turkey. 土耳其棉铃虫核多角体病毒新分离株(鳞翅目:夜蛾科)
IF 1.1 4区 生物学 Q3 BIOLOGY Pub Date : 2019-10-14 eCollection Date: 2019-01-01 DOI: 10.3906/biy-1902-64
Gözde Büşra Eroğlu, Remziye Nalçacioğlu, Zihni Demirbağ

This study reports a new Helicoverpa armigera nucleopolyhedrovirus (NPV) isolated from Heliothis peltigera (Denis & Schiffermuller), collected in the vicinity of Adana, Turkey. Infection was confirmed by tissue polymerase chain reaction and sequence analysis. Results showed that dead H. peltigera larvae contain Helicoverpa armigera nucleopolyhedrovirus. Thus, the isolate was named as HearNPV-TR. Microscopy studies indicated that occlusion bodies were 0.73 to 1.66 μm in diameter. The nucleocapsids are approximately 184 × 41 nm in size. The genome of HearNPV-TR was digested with KpnI and XhoI enzymes and calculated as 130.5 kb. Phylogenetic analysis showed that HearNPV-TR has close relation with the H. armigera SNPV-1073 China isolate. The Kimura analysis confirmed that the isolate is a variant of H. armigera NPV. Bioassays were performed using six different concentrations (1 × 103 to 1 × 108 occlusion bodies (OBs)/mL) on 2nd instar larvae of H. peltigera, H. armigera, Heliothis viriplaca, Heliothis nubigera. LC50 values were calculated to be 9.5 × 103, 1.9 × 104, 8.6 × 104 and 9.2 × 104 OBs/mL within 14 days, respectively. Results showed that it is a promising biocontrol agent against Heliothinae species.

本研究报道了从土耳其Adana附近采集的Heliothis peltigera (Denis & Schiffermuller)中分离到的一种新的棉铃虫核多角体病毒(NPV)。经组织聚合酶链反应和序列分析证实感染。结果表明,该蚊死亡幼虫含有棉铃虫核型多角体病毒。因此,该分离物被命名为HearNPV-TR。显微镜观察发现,闭塞体直径为0.73 ~ 1.66 μm。核衣壳的尺寸约为184 × 41 nm。HearNPV-TR基因组用KpnI和XhoI酶切,计算为130.5 kb。系统发育分析表明,HearNPV-TR与中国分离的棉铃虫SNPV-1073亲缘关系密切。Kimura的分析证实,该分离物是棉蚜NPV的一种变体。采用6种浓度(1 × 103 ~ 1 × 108个遮挡体/mL)对peltigera、H. armigera、Heliothis viriplaca、Heliothis nubigera 2龄幼虫进行生物测定。14 d内LC50值分别为9.5 × 103、1.9 × 104、8.6 × 104和9.2 × 104 OBs/mL。结果表明,它是一种很有前途的防蚊剂。
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引用次数: 0
Proteomic and physiological responses in mangrove Kandelia candel roots under short-term high-salinity stress 短期高盐度胁迫下红树红烛根的蛋白质组学和生理响应
IF 2.2 4区 生物学 Q3 BIOLOGY Pub Date : 2019-10-14 DOI: 10.3906/biy-1906-22
Jianhong Xing, Dezhuo Pan, Lingxia Wang, Fanglin Tan, Wei Chen
Kandelia candel is one of the mangrove species that are most resistant to environmental stress. As a typical nonsalt-secreting mangrove plant, K. candel is an ideal biological material to analyze the molecular mechanism of salt tolerance in woody plants. In this study, changes in protein abundance and expression profile in K. candel roots under high-salinity stress of 600 mmol L-1 NaCl were analyzed using isobaric tags for relative and absolute quantification (iTRAQ) assay. Moreover, the physiological parameters associated with metabolic pathways in which the differentially abundant proteins (DAPs) are involved were determined. A total of 5577 proteins were identified by iTRAQ analysis of the K. candel root proteins, of which 227 were DAPs with a fold change ratio >1.2 or a fold change ratio <0.83 and a P-value <0.05. A total of 227 DAPs consisting of 110 up-regulated and 117 down-regulated proteins were identified. Our Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the DAPs were primarily involved in biological processes including carbohydrate and energy metabolisms, stress response and defense, cell wall structure, and secondary metabolism. The results of the physiological parameters showed that their profile changes were consistent with those of the proteome analysis. The results of the proteome and physiological parameters showed that K. candel roots could resist high-salinity stress by maintaining a normal Embden-Meyerhof-Parnas and tricarboxylic acid (EMP-TCA) pathway, increasing the activities of various antioxidant enzymes and antioxidant contents, stabilizing the cell wall structure, and accumulating secondary metabolites such as triterpenoids.
坎德尔是最能抵抗环境压力的红树林物种之一。作为一种典型的不分泌盐的红树林植物,坎德尔是分析木本植物耐盐分子机制的理想生物材料。在本研究中,使用相对和绝对定量(iTRAQ)等压标签分析了在600 mmol L-1 NaCl的高盐度胁迫下坎德尔根的蛋白质丰度和表达谱的变化。此外,还确定了与代谢途径相关的生理参数,其中差异丰富的蛋白质(DAP)参与其中。通过对K.candel根蛋白的iTRAQ分析,共鉴定出5577种蛋白,其中227种是倍数变化率>1.2或倍数变化率<0.83且P值<0.05的DAP。共鉴定出227个DAP,由110个上调蛋白和117个下调蛋白组成。我们的基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析表明,DAP主要参与生物过程,包括碳水化合物和能量代谢、应激反应和防御、细胞壁结构和次级代谢。生理参数的结果表明,它们的图谱变化与蛋白质组分析的结果一致。蛋白质组和生理参数的结果表明,坎德尔根可以通过维持正常的Embden-Meyerhof-Parnas和三羧酸(EMP-TCA)途径,增加各种抗氧化酶的活性和抗氧化含量,稳定细胞壁结构,积累三萜等次生代谢产物来抵抗高盐度胁迫。
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引用次数: 8
A novel 1,4-naphthoquinone-derived compound induces apoptotic cell death in breast cancer cells 一种新型1,4-萘醌衍生化合物诱导乳腺癌细胞凋亡
IF 2.2 4区 生物学 Q3 BIOLOGY Pub Date : 2019-08-05 DOI: 10.3906/biy-1901-19
Didem Karakas, R. Akar, Zeliha Gökmen, N. Deniz, E. Ulukaya
Breast cancer is the most-diagnosed cancer type among women. The triple-negative subtype is an especially aggressive type of breast cancer. Although chemotherapy is almost the only option for the treatment of triple-negative breast cancer (TNBC), currently used chemotherapeutics are not effective enough, considering the poor survival rate of patients. Therefore, novel compounds need to be developed to improve survival rates. It has been known that quinonic compounds, which are found in nature, have antibacterial, antifungal, and antitumorigenic properties. Naphthoquinones are members of the quinone family and are widely used in research due to their promising properties. In this study, we evaluated the cytotoxic activity of a novel naphthoquinone-derived compound (1,4-naphthoquinone (1,4-NQ)) against two different breast cancer cells: a hormone-responsive cell line (MCF-7) and a triple-negative cell line (MDA-MB-231). As a result, 1,4-NQ decreased cell viability in both tested cell lines in a dose-dependent manner. Increased apoptotic markers (presence of pyknotic nuclei, annexin-V positivity, caspase 3/7 activity, and decreased mitochondrial membrane potential) and DNA damage were especially observed in MDA-MB-231 cells after treatment with the compound. Considering the promising cytotoxic effect of the compound, 1,4-NQ needs further evaluation as a potential candidate for the treatment of TNBC.
乳腺癌是女性中诊断最多的癌症类型。三阴性亚型是一种特别具有侵袭性的乳腺癌。虽然化疗几乎是治疗三阴性乳腺癌(TNBC)的唯一选择,但考虑到患者的生存率较低,目前使用的化疗药物不够有效。因此,需要开发新的化合物来提高生存率。众所周知,自然界中发现的醌类化合物具有抗菌、抗真菌和抗肿瘤的特性。萘醌类化合物是醌类化合物家族的一员,因其具有良好的性质而被广泛应用于研究中。在这项研究中,我们评估了一种新型萘醌衍生化合物(1,4-萘醌(1,4- nq))对两种不同的乳腺癌细胞的细胞毒活性:激素反应细胞系(MCF-7)和三阴性细胞系(MDA-MB-231)。结果,1,4- nq以剂量依赖的方式降低了两种被测细胞系的细胞活力。在MDA-MB-231细胞中,经该化合物处理后,凋亡标记物(核缩缩、膜联蛋白v阳性、caspase 3/7活性、线粒体膜电位降低)和DNA损伤明显增加。考虑到该化合物有希望的细胞毒性作用,1,4- nq作为治疗TNBC的潜在候选药物需要进一步评估。
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引用次数: 5
Characterizing microsatellite polymorphisms using assembly-based and mapping-based tools 使用基于组装和映射的工具表征微卫星多态性
IF 2.2 4区 生物学 Q3 BIOLOGY Pub Date : 2019-08-05 DOI: 10.3906/biy-1903-16
Gülfem Demi̇r, C. Alkan
Microsatellite polymorphism has always been a challenge for genome assembly and sequence alignment due to sequencing errors, short read lengths, and high incidence of polymerase slippage in microsatellite regions. Despite the information they carry being very valuable, microsatellite variations have not gained enough attention to be a routine step in genome sequence analysis pipelines. After the completion of the 1000 Genomes Project, which aimed to establish the most detailed genetic variation catalog for humans, the consortium released only two microsatellite prediction sets generated by two tools. Many other large research efforts have failed to shed light on microsatellite variations. We evaluated the performance of three different local assembly methods on three different experimental settings, focusing on genotype-based performance, coverage impact, and preprocessing including flanking regions. All these experiments supported our initial expectations on assembly. We also demonstrate that overlap-layout-consensus (OLC)-basedassembly methods show higher sensitivity to microsatellite variant calling when compared to a de Bruijn graph-based approach. We conclude that assembly with OLC is the better method for genotyping microsatellites. Our pipeline is available at https://github.com/gulfemd/STRAssembly.
微卫星多态性一直是基因组组装和序列比对的一个挑战,因为测序错误,短的读取长度,以及在微卫星区域高发生率的聚合酶滑移。尽管它们携带的信息非常有价值,但微卫星变异还没有得到足够的重视,不足以成为基因组序列分析管道中的常规步骤。在旨在建立最详细的人类遗传变异目录的千人基因组计划完成后,该联盟仅发布了由两种工具生成的两个微卫星预测集。许多其他大型研究工作都未能阐明微卫星的变化。我们在三种不同的实验环境下评估了三种不同的局部组装方法的性能,重点关注基于基因型的性能、覆盖影响和包括侧翼区域的预处理。所有这些实验都支持了我们最初对装配的期望。我们还证明,与基于de Bruijn图的方法相比,基于重叠布局共识(OLC)的装配方法对微卫星变体调用具有更高的灵敏度。结果表明,OLC组装是较好的微卫星基因分型方法。我们的管道可以在https://github.com/gulfemd/STRAssembly上找到。
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引用次数: 1
期刊
Turkish Journal of Biology
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