Abstract:
BACKGROUND:Modules of interacting components arranged in specific network topologies have evolved to perform a diverse array of cellular functions. For a network with a constant topological structure, its function within a cell may still be tuned by changing the number of instances of a particular component (e.g., gene copy number) or by modulating the intrinsic biochemical properties of a component (e.g., binding strength or catalytic efficiency). How such perturbations affect cellular response dynamics remains poorly understood. Here, we explored these effects in a common decision-making motif, cross-antagonism with autoregulation, by synthetically constructing this network in yeast. RESULTS:We employed the engineering design strategy of reuse to build this topology with a single protein building block, TetR, creating necessary components through TetR mutations and fusion partners. We then studied the impact of several topology-preserving perturbations - strength of cross-antagonism, number of operator sites in a promoter, and gene dosage - on decision-making behavior. We found that reducing TetR repression strength, which hinders cross-antagonism, resulted in a loss of mutually exclusive cell responses. Unexpectedly, increasing the number of operator sites also impeded decision-making exclusivity, which may be a consequence of the averaging effect that arises when multiple transcriptional activators and repressors are accommodated at a given locus. Stochastic simulations of this topology revealed that, even for networks with high TetR repression strength and a low number of operator sites, increasing gene dosage can reduce exclusivity in response dynamics. We further demonstrated this result experimentally by quantifying gene copy numbers in selected yeast clones with differing phenotypic responses. CONCLUSIONS:Our study illustrates how parameters that do not change the topological structure of a decision-making network can nonetheless exert significant influence on its response dynamics. These findings should further inform the study of native motifs, including the effects of topology-preserving mutations, and the robust engineering of synthetic networks.
journal_name
BMC Bioinformaticsjournal_title
BMC bioinformaticsauthors
Shah NA,Sarkar CAdoi
10.1186/s12859-019-2866-6subject
Has Abstractpub_date
2019-05-14 00:00:00pages
237issue
1issn
1471-2105pii
10.1186/s12859-019-2866-6journal_volume
20pub_type
杂志文章abstract:BACKGROUND:SNP genotyping microarrays have revolutionized the study of complex disease. The current range of commercially available genotyping products contain extensive catalogues of low frequency and rare variants. Existing SNP calling algorithms have difficulty dealing with these low frequency variants, as the under...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-158
更新日期:2014-05-23 00:00:00
abstract:UNLABELLED: BACKGROUND:Acquiring and exploring whole genome sequence information for a species under investigation is now a routine experimental approach. On most genome browsers, typically, only the DNA sequence, EST support, motif search results, and GO annotations are displayed. However, for many species, a growing...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-12-447
更新日期:2011-11-15 00:00:00
abstract:BACKGROUND:The field of protein sequence analysis is dominated by tools rooted in substitution matrices and alignments. A complementary approach is provided by methods of quantitative characterization. A major advantage of the approach is that quantitative properties defines a multidimensional solution space, where seq...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-017-1751-4
更新日期:2017-07-17 00:00:00
abstract:BACKGROUND:High throughput DNA/RNA sequencing has revolutionized biological and clinical research. Sequencing is widely used, and generates very large amounts of data, mainly due to reduced cost and advanced technologies. Quickly assessing the quality of giga-to-tera base levels of sequencing data has become a routine ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-3015-y
更新日期:2019-08-15 00:00:00
abstract:BACKGROUND:High-throughput sequencing can identify numerous potential genomic targets for microbial strain typing, but identification of the most informative combinations requires the use of computational screening tools. This paper describes novel software-- Automated Selection of Typing Target Subsets (AuSeTTS)--that...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-14-148
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:REX1 and REX2 are protein components of the RNA editing complex (the editosome) and function as exouridylylases. The exact roles of REX1 and REX2 in the editosome are unclear and the consequences of the presence of two related proteins are not fully understood. Here, a variety of computational studies were p...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-7-305
更新日期:2006-06-16 00:00:00
abstract:BACKGROUND:Understanding the community structure of microbes is typically accomplished by sequencing 16S ribosomal RNA (16S rRNA) genes. These community data can be represented by constructing a phylogenetic tree and comparing it with other samples using statistical methods. However, owing to high computational complex...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-11-332
更新日期:2010-06-18 00:00:00
abstract:BACKGROUND:Many statistical algorithms combine microarray expression data and genome sequence data to identify transcription factor binding motifs in the low eukaryotic genomes. Finding cis-regulatory elements in higher eukaryote genomes, however, remains a challenge, as searching in the promoter regions of genes with ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-7-44
更新日期:2006-01-26 00:00:00
abstract:BACKGROUND:A standardized and cost-effective molecular identification system is now an urgent need for Fungi owing to their wide involvement in human life quality. In particular the potential use of mitochondrial DNA species markers has been taken in account. Unfortunately, a serious difficulty in the PCR and bioinform...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-S6-S15
更新日期:2009-06-16 00:00:00
abstract:BACKGROUND:The analysis of DNA copy number variants (CNV) has increasing impact in the field of genetic diagnostics and research. However, the interpretation of CNV data derived from high resolution array CGH or NGS platforms is complicated by the considerable variability of the human genome. Therefore, tools for multi...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-1430-x
更新日期:2017-01-06 00:00:00
abstract:BACKGROUND:Over the last few years transcriptome sequencing (RNA-Seq) has almost completely taken over microarrays for high-throughput studies of gene expression. Currently, the most popular use of RNA-Seq is to identify genes which are differentially expressed between two or more conditions. Despite the importance of ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-014-0397-8
更新日期:2014-12-05 00:00:00
abstract:BACKGROUND:In bioinformatics community, many tasks associate with matching a set of protein query sequences in large sequence datasets. To conduct multiple queries in the database, a common used method is to run BLAST on each original querey or on the concatenated queries. It is inefficient since it doesn't exploit the...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-017-1938-8
更新日期:2017-11-21 00:00:00
abstract:BACKGROUND:Temporal gene expression profiles characterize the time-dynamics of expression of specific genes and are increasingly collected in current gene expression experiments. In the analysis of experiments where gene expression is obtained over the life cycle, it is of interest to relate temporal patterns of gene e...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-9-60
更新日期:2008-01-28 00:00:00
abstract:BACKGROUND:The most common method of identifying groups of functionally related genes in microarray data is to apply a clustering algorithm. However, it is impossible to determine which clustering algorithm is most appropriate to apply, and it is difficult to verify the results of any algorithm due to the lack of a gol...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-6-115
更新日期:2005-05-12 00:00:00
abstract:BACKGROUND:The secondary structure of RNA molecules is intimately related to their function and often more conserved than the sequence. Hence, the important task of searching databases for RNAs requires to match sequence-structure patterns. Unfortunately, current tools for this task have, in the best case, a running ti...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-12-214
更新日期:2011-05-27 00:00:00
abstract:BACKGROUND:Given a set of t n-length DNA sequences, q satisfying 0 < q ≤ 1, and l and d satisfying 0 ≤ d < l < n, the quorum planted motif search (qPMS) finds l-length strings that occur in at least qt input sequences with up to d mismatches and is mainly used to locate transcription factor binding sites in DNA sequenc...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-018-2242-y
更新日期:2018-06-18 00:00:00
abstract:BACKGROUND:We establish that the occurrence of protein folds among genomes can be accurately described with a Weibull function. Systems which exhibit Weibull character can be interpreted with reliability theory commonly used in engineering analysis. For instance, Weibull distributions are widely used in reliability, ma...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-5-101
更新日期:2004-07-26 00:00:00
abstract:BACKGROUND:Detection of periodically expressed genes from microarray data without use of known periodic and non-periodic training examples is an important problem, e.g. for identifying genes regulated by the cell-cycle in poorly characterised organisms. Commonly the investigator is only interested in genes expressed at...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-7-63
更新日期:2006-02-09 00:00:00
abstract:BACKGROUND:Accurately prioritizing candidate disease genes is an important and challenging problem. Various network-based methods have been developed to predict potential disease genes by utilizing the disease similarity network and molecular networks such as protein interaction or gene co-expression networks. Although...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-1317-x
更新日期:2016-11-10 00:00:00
abstract:BACKGROUND:A wide variety of short-read alignment programmes have been published recently to tackle the problem of mapping millions of short reads to a reference genome, focusing on different aspects of the procedure such as time and memory efficiency, sensitivity, and accuracy. These tools allow for a small number of ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-14-S11-S4
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Data are the evidentiary basis for scientific hypotheses, analyses and publication, for policy formation and for decision-making. They are essential to the evaluation and testing of results by peer scientists both present and future. There is broad consensus in the scientific and conservation communities tha...
journal_title:BMC bioinformatics
pub_type: 指南,杂志文章
doi:10.1186/1471-2105-12-S15-S1
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Parametric feature selection methods for machine learning and association studies based on genetic data are not robust with respect to outliers or influential observations. While rank-based, distribution-free statistics offer a robust alternative to parametric methods, their practical utility can be limited,...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-2869-3
更新日期:2019-06-13 00:00:00
abstract:BACKGROUND:In this paper, it is proposed an optimization approach for producing reduced alphabets for peptide classification, using a Genetic Algorithm. The classification task is performed by a multi-classifier system where each classifier (Linear or Radial Basis function Support Vector Machines) is trained using feat...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-9-45
更新日期:2008-01-24 00:00:00
abstract:BACKGROUND:Visualization software can expose previously undiscovered patterns in genomic data and advance biological science. RESULTS:The Genoviz Software Development Kit (SDK) is an open source, Java-based framework designed for rapid assembly of visualization software applications for genomics. The Genoviz SDK frame...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-266
更新日期:2009-08-25 00:00:00
abstract:BACKGROUND:Sharing sets of chemical data (e.g., chemical properties, docking scores, etc.) among collaborators with diverse skill sets is a common task in computer-aided drug design and medicinal chemistry. The ability to associate this data with images of the relevant molecular structures greatly facilitates scientifi...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-159
更新日期:2014-05-23 00:00:00
abstract:BACKGROUND:Feed-forward loops (FFLs), consisting of miRNAs, transcription factors (TFs) and their common target genes, have been validated to be important for the initialization and development of complex diseases, including cancer. Esophageal Carcinoma (ESCA) and Stomach Adenocarcinoma (STAD) are two types of malignan...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-3230-6
更新日期:2019-12-30 00:00:00
abstract:BACKGROUND:Inferring molecular pathway activity is an important step towards reducing the complexity of genomic data, understanding the heterogeneity in clinical outcome, and obtaining molecular correlates of cancer imaging traits. Increasingly, approaches towards pathway activity inference combine molecular profiles (...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-12-403
更新日期:2011-10-19 00:00:00
abstract:BACKGROUND:Although methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. Previously we have discussed the basic mechanisms of our novel method for structure compariso...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-11-138
更新日期:2010-03-17 00:00:00
abstract:BACKGROUND:The detection of genomic copy number alterations (CNA) in cancer based on SNP arrays requires methods that take into account tumour specific factors such as normal cell contamination and tumour heterogeneity. A number of tools have been recently developed but their performance needs yet to be thoroughly asse...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-13-192
更新日期:2012-08-07 00:00:00
abstract:BACKGROUND:Melanoma results in the vast majority of skin cancer deaths during the last decades, even though this disease accounts for only one percent of all skin cancers' instances. The survival rates of melanoma from early to terminal stages is more than fifty percent. Therefore, having the right information at the r...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-020-3351-y
更新日期:2020-03-11 00:00:00