Quantitative Biology最新文献

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Systems analysis of the "weights" of Bcl-2 and Mcl-1 in mitochondrial apoptosis pathwayestablishes a predictor for best drug combination ratio 对线粒体凋亡通路中Bcl-2和Mcl-1“权重”的系统分析建立了最佳药物组合比例的预测因子
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0237
Zongwei Guo, Fangkui Yin, Peiran Wang, T. Song, Zhichao Zhang
{"title":"Systems analysis of the \"weights\" of Bcl-2 and Mcl-1 in mitochondrial apoptosis pathwayestablishes a predictor for best drug combination ratio","authors":"Zongwei Guo, Fangkui Yin, Peiran Wang, T. Song, Zhichao Zhang","doi":"10.15302/j-qb-021-0237","DOIUrl":"https://doi.org/10.15302/j-qb-021-0237","url":null,"abstract":"Background : Inhibitors of B-cell CLL/lymphoma 2 (Bcl-2) family proteins have shown hope as antitumor drugs. While the notion that it is ef fi cient to coordinate, balance, and neutralize both arms of the anti-apoptotic Bcl-2 family has been validated in many cancer cells, the weights of the two arms contributing to apoptosis inhibition have not been explored. This study analyzed the best combination ratio for different Bcl-2 selective inhibitors. Methods : We used a previously established mathematical model to study the weights of Bcl-2 (representing both Bcl-2 and Bcl-xL in this study) and myeloid cell leukemia-1 (Mcl-1). Correlation and single-parameter sensitivity analysis were used to fi nd the major molecular determinants for Bcl-2 and Mcl-1 dependency, as well as their weights. Biological experiments were used to verify the mathematical model. Results : Bcl-2 protein level and Mcl-1 protein level, production, and degradation rates were the major molecular determinants for Bcl-2 and Mcl-1 dependency. The model gained agreement with the experimental assays for ABT-737/A-1210477 and ABT-737/compound 5 combination effect in MCF-7 and MDA-MB-231. Two sets of equations composed of Bcl-2 and Mcl-1 levels were obtained to predict the best combination ratio for Bcl-2 inhibitors with Mcl-1 inhibitors that stabilize and downregulate Mcl-1, respectively. Conclusions : The two sets of equations can be used as tools to bypass time-consuming and laborious experimental screening to predict the best drug combination ratio for treatment. Author summary: We used a mathematical model combined with experimental veri fi cation to quantitatively examine the contribution of the two arms of anti-apoptotic Bcl-2 proteins to apoptosis by weight. The correlation analysis and single-parameter sensitivity analysis showed that Bcl-2 protein level and Mcl-1 protein level, production, and degradation rates were the major molecular determinants. We gained two sets of equations as tools to bypass the time-consuming and laborious experimental screening to predict the best drug combination ratio for treatment. Biological experiments have veri fi ed the ef fi ciency of the tools in MCF-7, MDA-MB-231, OCI-AML3, and HCT-116 cells.","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"1 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67350896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Significance of differential allelic expression in phenotypic plasticity and evolutionary potential of microbial eukaryotes 差异等位基因表达在微生物真核生物表型可塑性和进化潜力中的意义
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0258
Ben P. Tatman, T. Mock, Taoyang Wu, C. Oosterhout
{"title":"Significance of differential allelic expression in phenotypic plasticity and evolutionary potential of microbial eukaryotes","authors":"Ben P. Tatman, T. Mock, Taoyang Wu, C. Oosterhout","doi":"10.15302/j-qb-021-0258","DOIUrl":"https://doi.org/10.15302/j-qb-021-0258","url":null,"abstract":"Background: Differential allelic expression (DAE) plays a key role in the regulation of many biological processes, and it may also play a role in adaptive evolution. Recently, environment-dependent DAE has been observed in species of marine phytoplankton, and most remarkably, alleles that showed the highest level of DAE also showed the fastest rate of evolution. Methods: To better understand the role of DAE in adaptive evolution and phenotypic plasticity, we developed a 2-D cellular automata model “ DAEsy-World ” that builds on the classical Daisyworld model. Results: Simulations show that DAE delineates the evolution of alternative alleles of a gene, enabling the two alleles to adapt to different environmental conditions and sub-functionalize. With DAE, the build-up of genetic polymorphisms within genes is driven by positive selection rather than strict neutral evolution, and this can enhance phenotypic plasticity. Moreover, in sexually reproducing organisms, DAE also increased the standing genetic variation, augmenting a species ’ adaptive evolutionary potential and ability to respond to fl uctuating and/or changing conditions ( cf . genetic assimilation). We furthermore show that DAE is likely to evolve in fl uctuating environmental conditions. Conclusions: DAE increases the adaptive evolutionary potential of both sexual and asexually reproducing organisms, and it may affect the pattern of nucleotide substitutions of genes. Author summary: In diploid organisms, the differential expression of the two alleles of a gene gives individuals more opportunities to adapt to fl uctuating environmental conditions, which is particularly bene fi cial for clonally reproducing species.","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"1 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67351048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular docking of cyanine and squarylium dyes with SARS-CoV-2 proteases NSP3, NSP5 and NSP12 菁和方英染料与SARS-CoV-2蛋白酶NSP3、NSP5和NSP12的分子对接
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0263
P. Pronkin, A. Tatikolov
{"title":"Molecular docking of cyanine and squarylium dyes with SARS-CoV-2 proteases NSP3, NSP5 and NSP12","authors":"P. Pronkin, A. Tatikolov","doi":"10.15302/j-qb-021-0263","DOIUrl":"https://doi.org/10.15302/j-qb-021-0263","url":null,"abstract":"Using molecular docking modeling, the noncovalent interaction of a large number of cyanine and squarylium dyes of various classes with SARS-CoV-2 coronavirus proteases has been studied. It has been found that electrostatic ligand-protein interactions (Coulomb interactions) can play an important role in the stability of noncovalent complexes. Based on the data obtained, the selection of dyes for further practical research has been carried out with the aim of developing spectral-fluorescent probes for detection of SARS-CoV-2. In addition, it is concluded that mesosubstituted thiacarbocyanines may be promising for use in photoinactivation of the coronavirus.","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"1 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67350868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent progress in research and application of engineered implanted cells for biomedical applications 生物医学工程植入细胞的研究与应用进展
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0253
{"title":"Recent progress in research and application of engineered implanted cells for biomedical applications","authors":"","doi":"10.15302/j-qb-021-0253","DOIUrl":"https://doi.org/10.15302/j-qb-021-0253","url":null,"abstract":"","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"1 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67350999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
The international Human Genome Project (HGP): A milestone for life sciences and humanity―The three stages and three major impacts of the HGP, and three contributions by China 国际人类基因组计划:生命科学与人类的里程碑——人类基因组计划的三个阶段、三个主要影响及中国的三个贡献
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0265
{"title":"The international Human Genome Project (HGP): A milestone for life sciences and humanity―The three stages and three major impacts of the HGP, and three contributions by China","authors":"","doi":"10.15302/j-qb-021-0265","DOIUrl":"https://doi.org/10.15302/j-qb-021-0265","url":null,"abstract":"","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"114 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67351008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
A Wonderful time – exciting progress made in the past 20 years in genetics powered by the Human Genome Project 一个美好的时代——在人类基因组计划的推动下,遗传学在过去20年里取得了令人兴奋的进展
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0273
{"title":"A Wonderful time – exciting progress made in the past 20 years in genetics powered by the Human Genome Project","authors":"","doi":"10.15302/j-qb-021-0273","DOIUrl":"https://doi.org/10.15302/j-qb-021-0273","url":null,"abstract":"","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67351075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mapping genetic variations in the first assembled human genome 绘制第一个组装的人类基因组的遗传变异图
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0277
{"title":"Mapping genetic variations in the first assembled human genome","authors":"","doi":"10.15302/j-qb-021-0277","DOIUrl":"https://doi.org/10.15302/j-qb-021-0277","url":null,"abstract":"","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"1 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67351134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Roles of statistical modeling in characterizing the genetic basis of human diseases and traits 统计建模在描述人类疾病和性状的遗传基础中的作用
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0283
{"title":"Roles of statistical modeling in characterizing the genetic basis of human diseases and traits","authors":"","doi":"10.15302/j-qb-021-0283","DOIUrl":"https://doi.org/10.15302/j-qb-021-0283","url":null,"abstract":"","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"207 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67351754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Polygenic risk scores: effect estimation and model optimization 多基因风险评分:效果估计与模型优化
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0238
Zijie Zhao, Jie Song, Tuo Wang, Q. Lu
{"title":"Polygenic risk scores: effect estimation and model optimization","authors":"Zijie Zhao, Jie Song, Tuo Wang, Q. Lu","doi":"10.15302/j-qb-021-0238","DOIUrl":"https://doi.org/10.15302/j-qb-021-0238","url":null,"abstract":"Background : Polygenic risk score (PRS) derived from summary statistics of genome-wide association studies (GWAS) is a useful tool to infer an individual ’ s genetic risk for health outcomes and has gained increasing popularity in human genetics research. PRS in its simplest form enjoys both computational ef fi ciency and easy accessibility, yet the predictive performance of PRS remains moderate for diseases and traits. Results : We provide an overview of recent advances in statistical methods to improve PRS ’ s performance by incorporating information from linkage disequilibrium, functional annotation, and pleiotropy. We also introduce model validation methods that fi ne-tune PRS using GWAS summary statistics. Conclusion : In this review, we showcase methodological advances and current limitations of PRS, and discuss several emerging issues in risk prediction research. Author summary: The prosperity of powerful genome-wide association studies (GWASs) has facilitated rapid development of polygenic risk score (PRS). Many post-GWAS PRS methods have been introduced to directly address the mediocre prediction accuracy of traditional PRS built upon marginal estimates from GWAS. This review fi rst summarizes PRS methods inspired by different biological concepts including LD, functional annotation, and pleiotropy to better quantify SNP effects. Then we introduce recent PRS frameworks that enable model optimization using summary statistics. Finally, we point out current pitfalls of risk prediction research. We expect emerging methods that address current challenges in the near future.","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"10 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67350979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Interpretable prediction of drug-cell line response by triple matrix factorization 三矩阵分解对药物细胞系反应的可解释性预测
IF 3.1 4区 生物学
Quantitative Biology Pub Date : 2021-01-01 DOI: 10.15302/j-qb-021-0259
{"title":"Interpretable prediction of drug-cell line response by triple matrix factorization","authors":"","doi":"10.15302/j-qb-021-0259","DOIUrl":"https://doi.org/10.15302/j-qb-021-0259","url":null,"abstract":"","PeriodicalId":45660,"journal":{"name":"Quantitative Biology","volume":"1 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67351119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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