A computational pipeline for identifying kinetic motifs to aid in the design and improvement of synthetic gene circuits

BACKGROUND: An increasing number of genetic components are available in several depositories of such components to facilitate synthetic biology research, but picking out those that will allow a designed circuit to achieve the specified function still requires multiple cycles of testing. Here, we addressed this problem by developing a computational pipeline to mathematically simulate a gene circuit for a comprehensive range and combination of the kinetic parameters of the biological components that constitute the gene circuit. RESULTS: We showed that, using a well-studied transcriptional repression cascade as an example, the sets of kinetic parameters that could produce the specified system dynamics of the gene circuit formed clusters of recurrent combinations, referred to as kinetic motifs, which appear to be associated with both the specific topology and specified dynamics of the circuit. Furthermore, the use of the resulting "handbook" of performance-ranked kinetic motifs in finding suitable circuit components was illustrated in two application scenarios. CONCLUSIONS: These results show that the computational pipeline developed here can provide a rational-based guide to aid in the design and improvement of synthetic gene circuits

Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks

<p>Abstract</p> <p>Background</p> <p>Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure.</p> <p>Results</p> <p>Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined.</p> <p>Conclusion</p> <p>Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks.</p

Reversible Data Hiding Scheme with High Embedding Capacity Using Semi-Indicator-Free Strategy

A novel reversible data-hiding scheme is proposed to embed secret data into a side-matched-vector-quantization- (SMVQ-) compressed image and achieve lossless reconstruction of a vector-quantization- (VQ-) compressed image. The rather random distributed histogram of a VQ-compressed image can be relocated to locations close to zero by SMVQ prediction. With this strategy, fewer bits can be utilized to encode SMVQ indices with very small values. Moreover, no indicator is required to encode these indices, which yields extrahiding space to hide secret data. Hence, high embedding capacity and low bit rate scenarios are deposited. More specifically, in terms of the embedding rate, the bit rate, and the embedding capacity, experimental results show that the performance of the proposed scheme is superior to those of the former data hiding schemes for VQ-based, VQ/SMVQ-based, and search-order-coding- (SOC-) based compressed images

In silico identification and comparative analysis of differentially expressed genes in human and mouse tissues

BACKGROUND: Screening for differentially expressed genes on the genomic scale and comparative analysis of the expression profiles of orthologous genes between species to study gene function and regulation are becoming increasingly feasible. Expressed sequence tags (ESTs) are an excellent source of data for such studies using bioinformatic approaches because of the rich libraries and tremendous amount of data now available in the public domain. However, any large-scale EST-based bioinformatics analysis must deal with the heterogeneous, and often ambiguous, tissue and organ terms used to describe EST libraries. RESULTS: To deal with the issue of tissue source, in this work, we carefully screened and organized more than 8 million human and mouse ESTs into 157 human and 108 mouse tissue/organ categories, to which we applied an established statistic test using different thresholds of the p value to identify genes differentially expressed in different tissues. Further analysis of the tissue distribution and level of expression of human and mouse orthologous genes showed that tissue-specific orthologs tended to have more similar expression patterns than those lacking significant tissue specificity. On the other hand, a number of orthologs were found to have significant disparity in their expression profiles, hinting at novel functions, divergent regulation, or new ortholog relationships. CONCLUSION: Comprehensive statistics on the tissue-specific expression of human and mouse genes were obtained in this very large-scale, EST-based analysis. These statistical results have been organized into a database, freely accessible at our website , for easy searching of human and mouse tissue-specific genes and for investigating gene expression profiles in the context of comparative genomics. Comparative analysis showed that, although highly tissue-specific genes tend to exhibit similar expression profiles in human and mouse, there are significant exceptions, indicating that orthologous genes, while sharing basic genomic properties, could result in distinct phenotypes

OPAAS: a web server for optimal, permuted, and other alternative alignments of protein structures

The large number of experimentally determined protein 3D structures is a rich resource for studying protein function and evolution, and protein structure comparison (PSC) is a key method for such studies. When comparing two protein structures, almost all currently available PSC servers report a single and sequential (i.e. topological) alignment, whereas the existence of good alternative alignments, including those involving permutations (i.e. non-sequential or non-topological alignments), is well known. We have recently developed a novel PSC method that can detect alternative alignments of statistical significance (alignment similarity P-value <10(−5)), including structural permutations at all levels of complexity. OPAAS, the server of this PSC method freely accessible at our website (), provides an easy-to-read hierarchical layout of output to display detailed information on all of the significant alternative alignments detected. Because these alternative alignments can offer a more complete picture on the structural, evolutionary and functional relationship between two proteins, OPAAS can be used in structural bioinformatics research to gain additional insight that is not readily provided by existing PSC servers

Protemot: prediction of protein binding sites with automatically extracted geometrical templates

Geometrical analysis of protein tertiary substructures has been an effective approach employed to predict protein binding sites. This article presents the Protemot web server that carries out prediction of protein binding sites based on the structural templates automatically extracted from the crystal structures of protein–ligand complexes in the PDB (Protein Data Bank). The automatic extraction mechanism is essential for creating and maintaining a comprehensive template library that timely accommodates to the new release of PDB as the number of entries continues to grow rapidly. The design of Protemot is also distinctive by the mechanism employed to expedite the analysis process that matches the tertiary substructures on the contour of the query protein with the templates in the library. This expediting mechanism is essential for providing reasonable response time to the user as the number of entries in the template library continues to grow rapidly due to rapid growth of the number of entries in PDB. This article also reports the experiments conducted to evaluate the prediction power delivered by the Protemot web server. Experimental results show that Protemot can deliver a superior prediction power than a web server based on a manually curated template library with insufficient quantity of entries. Availability:

Genomic DNA functions as a universal external standard in quantitative real-time PCR

Real-time quantitative PCR (qPCR) is a powerful tool for quantifying specific DNA target sequences. Although determination of relative quantity is widely accepted as a reliable means of measuring differences between samples, there are advantages to being able to determine the absolute copy numbers of a given target. One approach to absolute quantification relies on construction of an accurate standard curve using appropriate external standards of known concentration. We have validated the use of tissue genomic DNA as a universal external standard to facilitate quantification of any target sequence contained in the genome of a given species, addressing several key technical issues regarding its use. This approach was applied to validate mRNA expression of gene candidates identified from microarray data and to determine gene copies in transgenic mice. A simple method that can assist achieving absolute quantification of gene expression would broadly enhance the uses of real-time qPCR and in particular, augment the evaluation of global gene expression studies

AMiBA Wideband Analog Correlator

A wideband analog correlator has been constructed for the Yuan-Tseh Lee Array for Microwave Background Anisotropy. Lag correlators using analog multipliers provide large bandwidth and moderate frequency resolution. Broadband IF distribution, backend signal processing and control are described. Operating conditions for optimum sensitivity and linearity are discussed. From observations, a large effective bandwidth of around 10 GHz has been shown to provide sufficient sensitivity for detecting cosmic microwave background variations.Comment: 28 pages, 23 figures, ApJ in press

AMiBA: Broadband Heterodyne CMB Interferometry

The Y. T. Lee Array for Microwave Background (AMiBA) has reported the first science results on the detection of galaxy clusters via the Sunyaev Zel'dovich effect. The science objectives required small reflectors in order to sample large scale structures (20') while interferometry provided modest resolutions (2'). With these constraints, we designed for the best sensitivity by utilizing the maximum possible continuum bandwidth matched to the atmospheric window at 86-102GHz, with dual polarizations. A novel wide-band analog correlator was designed that is easily expandable for more interferometer elements. MMIC technology was used throughout as much as possible in order to miniaturize the components and to enhance mass production. These designs will find application in other upcoming astronomy projects. AMiBA is now in operations since 2006, and we are in the process to expand the array from 7 to 13 elements.Comment: 10 pages, 6 figures, ApJ in press; a version with high resolution figures available at http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/AMiBA7/mtc_highreso.pd

AMiBA: scaling relations between the integrated Compton-y and X-ray derived temperature, mass, and luminosity

We investigate the scaling relations between the X-ray and the thermal Sunyaev-Zel'dovich Effect (SZE) properties of clusters of galaxies, using data taken during 2007 by the Y.T. Lee Array for Microwave Background Anisotropy (AMiBA) at 94 GHz for the six clusters A1689, A1995, A2142, A2163, A2261, and A2390. The scaling relations relate the integrated Compton-y parameter Y_{2500} to the X-ray derived gas temperature T_{e}, total mass M_{2500}, and bolometric luminosity L_X within r_{2500}. Our results for the power-law index and normalization are both consistent with the self-similar model and other studies in the literature except for the Y_{2500}-L_X relation, for which a physical explanation is given though further investigation may be still needed. Our results not only provide confidence for the AMiBA project but also support our understanding of galaxy clusters.Comment: Accepted by ApJ; 8 pages, 3 figures, 5 table