Systems and Synthetic Biology最新文献_第2页

Knowledge-based discovery for designing CRISPR-CAS systems against invading mobilomes in thermophiles. 基于知识的发现:设计CRISPR-CAS系统对抗嗜热菌入侵的移动组。

Systems and Synthetic Biology Pub Date : 2015-09-01 Epub Date: 2015-08-06 DOI: 10.1007/s11693-015-9176-8

P Chellapandi, J Ranjani

{"title":"Knowledge-based discovery for designing CRISPR-CAS systems against invading mobilomes in thermophiles.","authors":"P Chellapandi, J Ranjani","doi":"10.1007/s11693-015-9176-8","DOIUrl":"https://doi.org/10.1007/s11693-015-9176-8","url":null,"abstract":"Clustered regularly interspaced short palindromic repeats (CRISPRs) are direct features of the prokaryotic genomes involved in resistance to their bacterial viruses and phages. Herein, we have identified CRISPR loci together with CRISPR-associated sequences (CAS) genes to reveal their immunity against genome invaders in the thermophilic archaea and bacteria. Genomic survey of this study implied that genomic distribution of CRISPR-CAS systems was varied from strain to strain, which was determined by the degree of invading mobiloms. Direct repeats found to be equal in some extent in many thermopiles, but their spacers were differed in each strain. Phylogenetic analyses of CAS superfamily revealed that genes cmr, csh, csx11, HD domain, devR were belonged to the subtypes of cas gene family. The members in cas gene family of thermophiles were functionally diverged within closely related genomes and may contribute to develop several defense strategies. Nevertheless, genome dynamics, geological variation and host defense mechanism were contributed to share their molecular functions across the thermophiles. A thermophilic archaean, Thermococcus gammotolerans and thermophilic bacteria, Petrotoga mobilis and Thermotoga lettingae have shown superoperons-like appearance to cluster cas genes, which were typically evolved for their defense pathways. A cmr operon was identified with a specific promoter in a thermophilic archaean, Caldivirga maquilingensis. Overall, we concluded that knowledge-based genomic survey and phylogeny-based functional assignment have suggested for designing a reliable genetic regulatory circuit naturally from CRISPR-CAS systems, acquired defense pathways, to thermophiles in future synthetic biology. ","PeriodicalId":22161,"journal":{"name":"Systems and Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11693-015-9176-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33994427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Design principles for robust oscillatory behavior. 稳健振荡行为的设计原则。

Systems and Synthetic Biology Pub Date : 2015-09-01 Epub Date: 2015-08-05 DOI: 10.1007/s11693-015-9178-6

Sebastian M Castillo-Hair, Elizabeth R Villota, Alberto M Coronado

{"title":"Design principles for robust oscillatory behavior.","authors":"Sebastian M Castillo-Hair, Elizabeth R Villota, Alberto M Coronado","doi":"10.1007/s11693-015-9178-6","DOIUrl":"https://doi.org/10.1007/s11693-015-9178-6","url":null,"abstract":"Oscillatory responses are ubiquitous in regulatory networks of living organisms, a fact that has led to extensive efforts to study and replicate the circuits involved. However, to date, design principles that underlie the robustness of natural oscillators are not completely known. Here we study a three-component enzymatic network model in order to determine the topological requirements for robust oscillation. First, by simulating every possible topological arrangement and varying their parameter values, we demonstrate that robust oscillators can be obtained by augmenting the number of both negative feedback loops and positive autoregulations while maintaining an appropriate balance of positive and negative interactions. We then identify network motifs, whose presence in more complex topologies is a necessary condition for obtaining oscillatory responses. Finally, we pinpoint a series of simple architectural patterns that progressively render more robust oscillators. Together, these findings can help in the design of more reliable synthetic biomolecular networks and may also have implications in the understanding of other oscillatory systems. ","PeriodicalId":22161,"journal":{"name":"Systems and Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11693-015-9178-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33925345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Quantification of the gene silencing performances of rationally-designed synthetic small RNAs. 合理设计的合成小rna基因沉默性能的定量分析。

Systems and Synthetic Biology Pub Date : 2015-09-01 Epub Date: 2015-08-07 DOI: 10.1007/s11693-015-9177-7

Ilaria Massaiu, Lorenzo Pasotti, Michela Casanova, Nicolò Politi, Susanna Zucca, Maria Gabriella Cusella De Angelis, Paolo Magni

{"title":"Quantification of the gene silencing performances of rationally-designed synthetic small RNAs.","authors":"Ilaria Massaiu, Lorenzo Pasotti, Michela Casanova, Nicolò Politi, Susanna Zucca, Maria Gabriella Cusella De Angelis, Paolo Magni","doi":"10.1007/s11693-015-9177-7","DOIUrl":"https://doi.org/10.1007/s11693-015-9177-7","url":null,"abstract":"Small RNAs (sRNAs) are genetic tools for the efficient and specific tuning of target genes expression in bacteria. Inspired by naturally occurring sRNAs, recent works proposed the use of artificial sRNAs in synthetic biology for predictable repression of the desired genes. Their potential was demonstrated in several application fields, such as metabolic engineering and bacterial physiology studies. Guidelines for the rational design of novel sRNAs have been recently proposed. According to these guidelines, in this work synthetic sRNAs were designed, constructed and quantitatively characterized in Escherichia coli. An sRNA targeting the reporter gene RFP was tested by measuring the specific gene silencing when RFP was expressed at different transcription levels, under the control of different promoters, in different strains, and in single-gene or operon architecture. The sRNA level was tuned by using plasmids maintained at different copy numbers. Results demonstrated that RFP silencing worked as expected in an sRNA and mRNA expression-dependent fashion. A mathematical model was used to support sRNA characterization and to estimate an efficiency-related parameter that can be used to compare the performance of the designed sRNA. Gene silencing was also successful when RFP was placed in a two-gene synthetic operon, while the non-target gene (GFP) in the operon was not considerably affected. Finally, silencing was evaluated for another designed sRNA targeting the endogenous lactate dehydrogenase gene. The quantitative study performed in this work elucidated interesting performance-related and context-dependent features of synthetic sRNAs that will strongly support predictable gene silencing in disparate basic or applied research studies. ","PeriodicalId":22161,"journal":{"name":"Systems and Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11693-015-9177-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33994428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Variation of swimming speed enhances the chemotactic migration of Escherichia coli. 游泳速度的变化可增强大肠杆菌的趋化迁移。

Systems and Synthetic Biology Pub Date : 2015-09-01 Epub Date: 2015-07-09 DOI: 10.1007/s11693-015-9174-x

R V S Uday Bhaskar, Richa Karmakar, Deepti Deepika, Mahesh S Tirumkudulu, K V Venkatesh

{"title":"Variation of swimming speed enhances the chemotactic migration of Escherichia coli.","authors":"R V S Uday Bhaskar, Richa Karmakar, Deepti Deepika, Mahesh S Tirumkudulu, K V Venkatesh","doi":"10.1007/s11693-015-9174-x","DOIUrl":"10.1007/s11693-015-9174-x","url":null,"abstract":"Studies on chemotaxis of Escherichia coli have shown that modulation of tumble frequency causes a net drift up the gradient of attractants. Recently, it has been demonstrated that the bacteria is also capable of varying its runs speed in uniform concentration of attractant. In this study, we investigate the role of swimming speed on the chemotactic migration of bacteria. To this end, cells are exposed to gradients of a non-metabolizable analogue of glucose which are sensed via the Trg sensor. When exposed to a gradient, the cells modulate their tumble duration, which is accompanied with variation in swimming speed leading to drift velocities that are much higher than those achieved through the modulation of the tumble duration alone. We use an existing intra-cellular model developed for the Tar receptor and incorporate the variation of the swimming speed along with modulation of tumble frequency to predict drift velocities close to the measured values. The main implication of our study is that E. coli not only modulates the tumble frequency, but may also vary the swimming speed to affect chemotaxis and thereby efficiently sample its nutritionally rich environment. ","PeriodicalId":22161,"journal":{"name":"Systems and Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531881/pdf/11693_2015_Article_9174.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33994426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erratum to: Diversity oriented synthesis for novel anti-malarials 新的抗疟疾药物的多样性导向合成的勘误

Systems and Synthetic Biology Pub Date : 2015-07-18 DOI: 10.1007/s11693-015-9175-9

C. Bathula, Shailja Singh, S. Sen

引用次数: 0

Mathematical model of flagella gene expression dynamics in Salmonella enterica serovar typhimurium. 肠炎沙门氏菌鼠伤寒血清型鞭毛基因表达动态的数学模型。

Systems and Synthetic Biology Pub Date : 2015-06-01 Epub Date: 2015-02-04 DOI: 10.1007/s11693-015-9160-3

Kirti Jain, Amit Pradhan, Chaitanya Mokashi, Supreet Saini

引用次数: 6

CARDIO-PRED: an in silico tool for predicting cardiovascular-disorder associated proteins. CARDIO-PRED:一个预测心血管疾病相关蛋白的计算机工具。

Systems and Synthetic Biology Pub Date : 2015-06-01 Epub Date: 2015-03-14 DOI: 10.1007/s11693-015-9164-z

Prerna Jain, Nitin Thukral, Lokesh Kumar Gahlot, Yasha Hasija

{"title":"CARDIO-PRED: an in silico tool for predicting cardiovascular-disorder associated proteins.","authors":"Prerna Jain, Nitin Thukral, Lokesh Kumar Gahlot, Yasha Hasija","doi":"10.1007/s11693-015-9164-z","DOIUrl":"https://doi.org/10.1007/s11693-015-9164-z","url":null,"abstract":"Interactions between proteins largely govern cellular processes and this has led to numerous efforts culminating in enormous information related to the proteins, their interactions and the function which is determined by their interactions. The main concern of the present study is to present interface analysis of cardiovascular-disorder (CVD) related proteins to shed lights on details of interactions and to emphasize the importance of using structures in network studies. This study combines the network-centred approach with three dimensional studies to comprehend the fundamentals of biology. Interface properties were used as descriptors to classify the CVD associated proteins and non-CVD associated proteins. Machine learning algorithm was used to generate a classifier based on the training set which was then used to predict potential CVD related proteins from a set of polymorphic proteins which are not known to be involved in any disease. Among several classifying algorithms applied to generate models, best performance was achieved using Random Forest with an accuracy of 69.5 %. The tool named CARDIO-PRED, based on the prediction model is present at http://www.genomeinformatics.dce.edu/CARDIO-PRED/. The predicted CVD related proteins may not be the causing factor of particular disease but can be involved in pathways and reactions yet unknown to us thus permitting a more rational analysis of disease mechanism. Study of their interactions with other proteins can significantly improve our understanding of the molecular mechanism of diseases. ","PeriodicalId":22161,"journal":{"name":"Systems and Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11693-015-9164-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33176892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Cheminformatics models based on machine learning approaches for design of USP1/UAF1 abrogators as anticancer agents. 基于机器学习方法的USP1/UAF1拮抗剂设计的化学信息学模型。

Systems and Synthetic Biology Pub Date : 2015-06-01 Epub Date: 2015-01-30 DOI: 10.1007/s11693-015-9162-1

Divya Wahi, Salma Jamal, Sukriti Goyal, Aditi Singh, Ritu Jain, Preeti Rana, Abhinav Grover

{"title":"Cheminformatics models based on machine learning approaches for design of USP1/UAF1 abrogators as anticancer agents.","authors":"Divya Wahi, Salma Jamal, Sukriti Goyal, Aditi Singh, Ritu Jain, Preeti Rana, Abhinav Grover","doi":"10.1007/s11693-015-9162-1","DOIUrl":"https://doi.org/10.1007/s11693-015-9162-1","url":null,"abstract":"Cancer cells have upregulated DNA repair mechanisms, enabling them survive DNA damage induced during repeated rapid cell divisions and targeted chemotherapeutic treatments. Cancer cell proliferation and survival targeting via inhibition of DNA repair pathways is currently a very promiscuous anti-tumor approach. The deubiquitinating enzyme, USP1 is known to promote DNA repair via complexing with UAF1. The USP1/UAF1 complex is responsible for regulating DNA break repair pathways such as trans-lesion synthesis pathway, Fanconi anemia pathway and homologous recombination. Thus, USP1/UAF1 inhibition poses as an efficient anti-cancer strategy. The recently made available high throughput screen data for anti USP1/UAF1 activity prompted us to compute bioactivity predictive models that could help in screening for potential USP1/UAF1 inhibitors having anti-cancer properties. The current study utilizes publicly available high throughput screen data set of chemical compounds evaluated for their potential USP1/UAF1 inhibitory effect. A machine learning approach was devised for generation of computational models that could predict for potential anti USP1/UAF1 biological activity of novel anticancer compounds. Additional efficacy of active compounds was screened by applying SMARTS filter to eliminate molecules with non-drug like features. The structural fragment analysis was further performed to explore structural properties of the molecules. We demonstrated that modern machine learning approaches could be efficiently employed in building predictive computational models and their predictive performance is statistically accurate. The structure fragment analysis revealed the structures that could play an important role in identification of USP1/UAF1 inhibitors. ","PeriodicalId":22161,"journal":{"name":"Systems and Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11693-015-9162-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33304194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

In silico study of peptide inhibitors against BACE 1. 抗BACE 1肽抑制剂的计算机实验研究。

Systems and Synthetic Biology Pub Date : 2015-06-01 Epub Date: 2015-03-19 DOI: 10.1007/s11693-015-9169-7

Navya Raj, Agnes Helen, N Manoj, G Harish, Vipin Thomas, Shailja Singh, Seema Sehrawat, Shaguna Seth, Achuthsankar S Nair, Abhinav Grover, Pawan K Dhar

{"title":"In silico study of peptide inhibitors against BACE 1.","authors":"Navya Raj, Agnes Helen, N Manoj, G Harish, Vipin Thomas, Shailja Singh, Seema Sehrawat, Shaguna Seth, Achuthsankar S Nair, Abhinav Grover, Pawan K Dhar","doi":"10.1007/s11693-015-9169-7","DOIUrl":"https://doi.org/10.1007/s11693-015-9169-7","url":null,"abstract":"Peptides are increasingly used as inhibitors of various disease specific targets. Several naturally occurring and synthetically developed peptides are undergoing clinical trials. Our work explores the possibility of reusing the non-expressing DNA sequences to predict potential drug-target specific peptides. Recently, we experimentally demonstrated the artificial synthesis of novel proteins from non-coding regions of Escherichia coli genome. In this study, a library of synthetic peptides (Synpeps) was constructed from 2500 intergenic E. coli sequences and screened against Beta-secretase 1 protein, a known drug target for Alzheimer's disease (AD). Secondary and tertiary protein structure predictions followed by protein-protein docking studies were performed to identify the most promising enzyme inhibitors. Interacting residues and favorable binding poses of lead peptide inhibitors were studied. Though initial results are encouraging, experimental validation is required in future to develop efficient target specific inhibitors against AD. ","PeriodicalId":22161,"journal":{"name":"Systems and Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11693-015-9169-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33176893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

On Brucella pathogenesis: looking for the unified challenge in systems and synthetic biology. 论布鲁氏菌的发病机制:寻找系统生物学和合成生物学的统一挑战。

Systems and Synthetic Biology Pub Date : 2015-06-01 Epub Date: 2014-12-21 DOI: 10.1007/s11693-014-9158-2

Srikanth Chiliveru, Mahesh Appari, Prashanth Suravajhala

引用次数: 5