Hierarchy Of Domains Research Articles

Hierarchy of Protein Loop-Lock Structures: A New Server for the Decomposition of a Protein Structure into a Set of Closed Loops

HoPLLS (Hierarchy of protein loop-lock structures) (http://leah.haifa.ac.il/~skogan/Apache/mydata1/main.html) is a web server that identifies closed loops - a structural basis for protein domain hierarchy. The server is based on the loop-and-lock theory for structural organisation of natural proteins. We describe this web server, the algorithms for the decomposition of a 3D protein into loops and the results of scientific investigations into a structural "alphabet" of loops and locks.

K-Anonymization using Multidimensional Suppression for Data De-identification

searching methods have advanced the increased risk of privacy disclosure makes it important to protect privacy of user during data publishing. Many of the algorithms used for the data de-identification are not efficient because resulted dataset can easily linked with the public database and it reveals the users identity. One of the method uses for protecting the privacy of user is to apply anonymization algorithms. TDS and TDR using generalization of method to anonymized the dataset. Major drawback as these algorithm is they requires a manually generated domain hierarchy taxonomy for every quasi-identifier in the data set on which k- anonymity has to be performed. Therefore, in this paper we propose new approach which will makes use of suppression based k-anonymization method to allow data publisher to de- identify datasets and in this method only certain attributes from record are suppressed based on values other attributes. As suppression method is used in algorithm, it does not required manually created taxonomy tree of quasi-identifiers. We applied this algorithm on 3 different data sets to evaluate its accuracy as compared to other k-anonymity generalization algorithms. It is found that predicative performance of this algorithm is better than existing generalization methods. This method is expected to provide privacy and accuracy measures to data publishers.

Automated hierarchical classification of protein domain subfamilies based on functionally-divergent residue signatures

BackgroundThe NCBI Conserved Domain Database (CDD) consists of a collection of multiple sequence alignments of protein domains that are at various stages of being manually curated into evolutionary hierarchies based on conserved and divergent sequence and structural features. These domain models are annotated to provide insights into the relationships between sequence, structure and function via web-based BLAST searches.ResultsHere we automate the generation of conserved domain (CD) hierarchies using a combination of heuristic and Markov chain Monte Carlo (MCMC) sampling procedures and starting from a (typically very large) multiple sequence alignment. This procedure relies on statistical criteria to define each hierarchy based on the conserved and divergent sequence patterns associated with protein functional-specialization. At the same time this facilitates the sequence and structural annotation of residues that are functionally important. These statistical criteria also provide a means to objectively assess the quality of CD hierarchies, a non-trivial task considering that the protein subgroups are often very distantly related—a situation in which standard phylogenetic methods can be unreliable. Our aim here is to automatically generate (typically sub-optimal) hierarchies that, based on statistical criteria and visual comparisons, are comparable to manually curated hierarchies; this serves as the first step toward the ultimate goal of obtaining optimal hierarchical classifications. A plot of runtimes for the most time-intensive (non-parallelizable) part of the algorithm indicates a nearly linear time complexity so that, even for the extremely large Rossmann fold protein class, results were obtained in about a day.ConclusionsThis approach automates the rapid creation of protein domain hierarchies and thus will eliminate one of the most time consuming aspects of conserved domain database curation. At the same time, it also facilitates protein domain annotation by identifying those pattern residues that most distinguish each protein domain subgroup from other related subgroups.

Hierarchy between the transmembrane and cytoplasmic domains in the regulation of syndecan-4 functions

Syndecan-4, a transmembrane heparan sulfate proteoglycan, plays a critical role in cell adhesion. Both the transmembrane and cytoplasmic domains of syndecan-4 are known to contribute to its functions, but the regulatory mechanisms underlying the functional interplay between the two domains were previously unclear. Here, we examined the functional relationship between these two domains. Fluorescence resonance energy transfer (FRET)-based assays showed that syndecan-4 expression enhanced RhoA activation. Furthermore, rat embryonic fibroblasts (REFs) plated on fibronectin fragments lacking the heparin-binding domain that interacts with syndecan-4 showed much lower RhoA activation than that in cells plated on full-length fibronectin, indicating that RhoA is involved in syndecan-4-mediated cell adhesion signaling. Syndecan-4 mutants defective in transmembrane domain-induced oligomerization and syndecan-4 phosphorylation-mimicking cytoplasmic domain mutants showed decreases in RhoA activation and RhoA-related functions, such as adhesion, spreading and focal adhesion formation, and subsequent increase in cell migration, but the inhibitory effect was much higher in cells expressing the transmembrane domain mutants. The cytoplasmic domain mutants (but not the transmembrane domain mutants) retained the capacity to form SDS-resistant dimers, and the cytoplasmic mutants showed less inhibition of syndecan-4-mediated protein kinase C activation compared to the transmembrane domain mutants. Finally, cytoplasmic domain activation failed to overcome the inhibition conferred by mutation of the transmembrane domain. Taken together, these data suggest that the transmembrane domain plays a major role in regulating syndecan-4 functions, and further show that a domain hierarchy exists in the regulation of syndecan-4.

K-anonymised reducts

Privacy-preserving data mining aims to prevent the exposure of sensitive information as a result of mining algorithms. This is commonly achieved by data anonymisation. One way to anonymise data is by adherence to the k-anonymity concept which requires that the probability to identify an individual by linking databases does not exceed 1/k. In this paper, we propose an algorithm which utilises rough set theory to achieve k-anonymity. The basic idea is to partition the original dataset into several disjoint reducts such that each one of them adheres to k-anonymity. We show that it is easier to make each reduct comply with k-anonymity if it does not contain all quasi-identifier attributes. Moreover, our procedure ensures that even if the attacker attempts to rejoin the reducts, the k-anonymity is still preserved. Unlike other algorithms that achieve k-anonymity, the proposed method requires no prior knowledge of the domain hierarchy taxonomy.

Attitudes to Arabic language policies in Israel

The paper reports the findings of a survey study which examined attitudes towards a range of language policies for the Arabic language in Israel. Arabic is an official language in Israel as a result of a Mandatory Order (1922) which dictates comprehensive Hebrew-Arabic bilingual conduct by state authorities. In practice, Arabic’s public position in Israel is marginal, and Hebrew is the dominant language in Israeli public spheres. Arabic speakers, a national indigenous minority, and Jewish immigrants from the Former Soviet Union, form the two largest language-minority groups in Israel. The study explored attitudes concerning (1) the use of Arabic in three public domains (government services, public television, and teaching of Arabic in Jewish schools), (2) a Hebrew-Arabic bilingual model, and (3) a multilingual model addressing language minorities in Israel in general. Respondents were 466 university and college students, Jews and Arabs, divided into five subgroups along linguistic, ethnic and religious lines. The main findings indicated (1) a clear hierarchy of language policy domains among all five subgroups, with ‘government services’ being the most favored domain; (2) a tendency among Jewish respondents to favor a multilingual policy over a Hebrew-Arabic bilingual one; and (3) a language minority element (non-native Hebrew speakers), overshadowed by the ethnic-religious (Jewish-Arab) element.

Assessment of Functional Caregiving in Homes With a Child With an Intellectual Disability

The authors report on the nature of assessing functional caregiving (FC) via three studies, conducted by a university–public preschool collaboration that was designed to measure mothers' confidence to care for children with intellectual disabilities in their homes. Caregiving of children with intellectual disabilities was conceptualized in terms of a task hierarchy that occurs in a complex, multi-level sociocultural ecology. Rating scale items were developed to survey mothers' caregiving confidence in this ecology, which were analyzed with a Rasch model. Raw ratings were transformed to an axiomatically strong, objective, unidimensional scale, and the obtained task difficulties conformed to a three-tier caregiving hierarchy of advocacy, personal caregiving, and community relations domains. Hierarchical regression of task difficulties on item components defined by FC domains was consistent with an ecological model (R2 > 0.60). The task hierarchy was also found to be consistent with humanistic psychology principles. When FC measurement properties were compared between suburban and urban mothers, as well as mothers of educationally at risk and special needs children, psychometric reliability was high (>0.90). Validity studies confirmed FC functional relations with mothers' health, age, and economic status. In general, these studies found that mothers' self-confidence measures were valid and reliable, but noted future studies are needed to link FC measures directly to competency and home caregiving quality. Future research should also explore replication of core items across other disabilities and chronic diseases, as well as applicability to objective caregiving standard setting.

Microstructure basis for strong piezoelectricity in Pb-free Ba(Zr0.2Ti0.8)O3-(Ba0.7Ca0.3)TiO3 ceramics

In this letter, we use transmission electron microscopy to study the microstructure feature of recently reported Pb-free piezoceramic Ba(Zr0.2Ti0.8)O3-x(Ba0.7Ca0.3)TiO3 across its piezoelectricity-optimal morphotropic phase boundary (MPB) by varying composition and temperature, respectively. The domain structure evolutions during such processes show that in MPB regime, the domains become miniaturized down to nanometer size with a domain hierarchy, which coincides with the d33-maximum region. Further convergent beam electron diffraction measurement shows that rhombohedral and tetragonal crystal symmetries coexist among the miniaturized domains. Strong piezoelectricity reported in such a system is due to easy polarization rotation between the coexisting nano-scale tetragonal and rhombohedral domains.

Real-time large-deformation substructuring

This paper shows a method to extend 3D nonlinear elasticity model reduction to open-loop multi-level reduced deformable structures. Given a volumetric mesh, we decompose the mesh into several subdomains, build a reduced deformable model for each domain, and connect the domains using inertia coupling. This makes model reduction deformable simulations much more versatile: localized deformations can be supported without prohibitive computational costs, parts can be re-used and precomputation times shortened. Our method does not use constraints, and can handle large domain rigid body motion in addition to large deformations, due to our derivation of the gradient and Hessian of the rotation matrix in polar decomposition. We show real-time examples with multi-level domain hierarchies and hundreds of reduced degrees of freedom.

Tertiary Interactions Maintain the Balance of Stability, Folding Efficiency and Speed in a Large Catalytic Bacterial RNA

Like their protein counterparts, many non-coding RNAs, such as ribozymes, must fold into a unique 3D structure suited for their biological actions. These RNA structures are stabilized by an array of conserved tertiary interactions between residues far apart in sequence. However, the extent of thermodynamic coupling between tertiary interactions in RNA is little understood. To probe the basis for cooperative folding in RNA, we perturbed the folding energetics of a bacterial group I ribozyme with mutations that disrupt five conserved tertiary interaction sites. The assembly of core helices into compact native-like intermediates was measured by SAXS and native PAGE. Formation of the native state was probed with activity assays and hydroxyl radical footprinting of the RNA backbone. Although all of the mutants were catalytically active, their folding landscapes were significantly changed. Single mutations destabilized the compact intermediates and disrupted the thermodynamic link between tertiary interactions measured through double mutant cycles. Native PAGE and footprinting showed that loss of a single tertiary interaction affected the stability of other structural domains due to competition with non-native structures. Stopped-flow SAXS and hydroxyl radical footprinting with millisecond resolution showed that disruption of tertiary interactions does not hamper the rapid initial collapse of the RNA chain, but changes the folding hierarchy of the structural domains and the structures of populated intermediates. These results shed light on the interplay of the conserved tertiary interactions and electrostatic forces in the folding of large RNA molecules and delineate the mechanisms by which evolved RNA sequences determine the outcome of an otherwise nonspecific counterion-mediated collapse.

Identification of hierarchy of dynamic domains in proteins: comparison of HDWA and HCCP techniques

Identification of hierarchy of dynamic domains in proteins: comparison of HDWA and HCCP techniques

Abstract 95: Phylogenetic classification, structural evolution, and functional divergence of the ABC-type transporters: Inferences derived from CDTree/Cn3D software applications

Abstract The NCBI's Conserved Domain Database (CDD; http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml), is a collection of annotated multiple sequence alignment models representing ancient conserved protein domains, basic units of protein function and protein evolution. Domain models are annotated with functional sites and can be viewed as sequence alignments together with corresponding 3D structure using the CDTree/Cn3D software applications. CDTree/Cn3D is a domain hierarchy editor which lets the user view and examine conserved domain hierarchies interactively and in great detail. A domain hierarchy is a structured collection of domain models reflecting the domain family's molecular evolution. Here we present our current, functionally annotated evolutionary classifications of the nucleotide-binding domain, transmembrane domain, and periplasmic binding proteins of the ABC (ATP binding cassette)-type transport systems which are involved in the transport of a wide variety of substrates such as sugars, ions, peptides, and more complex organic molecules across membranes. Mutations in ABC transporters cause or contribute to multi-drug resistance, cystic fibrosis, and a range of other human diseases. Using CDTree/Cn3D functionality, subfamilies present in diverse organisms were inferred from the multiple sequence alignments, phylogenetic trees, and the domain architectures of the proteins involved. Furthermore subfamilies, some of which are only comprised of uncharacterized proteins, were annotated with molecular and cellular function and the location of conserved sites, as available in the literature and evident from protein 3D structure. We demonstrate the utility of CDTree/Cn3D in studying the molecular evolution of protein and domain families, and in accelerating the discovery of orthologous groups. CDTree/Cn3D are freely available for download via the CDD website. A version of CDTree, which supports both Mac OSX and Windows operating systems, has recently been made available. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 95.

Identifying the Hierarchy of Dynamic Domains in Proteins Using the Data of Molecular Dynamics Simulations

The Hierarchical Domain-Wise Alignment (HDWA) technique of domain identification in proteins is presented. HDWA is designed to identify hierarchically organized dynamic domains in proteins using the MD trajectories by eliminating systematic motions from MD trajectories recursively in a model-free manner. The method is tested on the proteins from different structural classes.

New technique of identifying the hierarchy of dynamic domains in proteins using a method of molecular dynamics simulations

Keywords: dynamic domains, domain identification, Hierarchical Domain-Wise Alignment, molecular dynamics

Efficient Multidimensional Suppression for K-Anonymity

Many applications that employ data mining techniques involve mining data that include private and sensitive information about the subjects. One way to enable effective data mining while preserving privacy is to anonymize the data set that includes private information about subjects before being released for data mining. One way to anonymize data set is to manipulate its content so that the records adhere to k-anonymity. Two common manipulation techniques used to achieve k-anonymity of a data set are generalization and suppression. Generalization refers to replacing a value with a less specific but semantically consistent value, while suppression refers to not releasing a value at all. Generalization is more commonly applied in this domain since suppression may dramatically reduce the quality of the data mining results if not properly used. However, generalization presents a major drawback as it requires a manually generated domain hierarchy taxonomy for every quasi-identifier in the data set on which k-anonymity has to be performed. In this paper, we propose a new method for achieving k-anonymity named K-anonymity of Classification Trees Using Suppression (kACTUS). In kACTUS, efficient multidimensional suppression is performed, i.e., values are suppressed only on certain records depending on other attribute values, without the need for manually produced domain hierarchy trees. Thus, in kACTUS, we identify attributes that have less influence on the classification of the data records and suppress them if needed in order to comply with k-anonymity. The kACTUS method was evaluated on 10 separate data sets to evaluate its accuracy as compared to other k-anonymity generalization- and suppression-based methods. Encouraging results suggest that kACTUS' predictive performance is better than that of existing k-anonymity algorithms. Specifically, on average, the accuracies of TDS, TDR, and kADET are lower than kACTUS in 3.5, 3.3, and 1.9 percent, respectively, despite their usage of manually defined domain trees. The accuracy gap is increased to 5.3, 4.3, and 3.1 percent, respectively, when no domain trees are used.

Self-generated Domains of Quality of Life in Children with and Without Cerebral Palsy

This study was conducted to demonstrate feasibility of utilizing a modified SEIQoL-DW with children by examining self-generated domains of quality of life in children with and without cerebral palsy. Study samples were children, ages 6-12, (mean 8.9, SD 1.8) including 41 children with cerebral palsy (CP) and 60 children who were age and gender matched peers without disability. Quality of life was assessed with a modified Schedule for the Evaluation of Individual Quality of Life-Direct Weight (SEIQoL-DW). Group differences in overall ratings of quality of life were not significant; however, there were significant group differences in the frequency and hierarchy of self-generated domains. Within the group with CP, functional ability was not associated with quality of life.

Gene3D: merging structure and function for a Thousand genomes

Over the last 2 years the Gene3D resource has been significantly improved, and is now more accurate and with a much richer interactive display via the Gene3D website (http://gene3d.biochem.ucl.ac.uk/). Gene3D provides accurate structural domain family assignments for over 1100 genomes and nearly 10 000 000 proteins. A hidden Markov model library, constructed from the manually curated CATH structural domain hierarchy, is used to search UniProt, RefSeq and Ensembl protein sequences. The resulting matches are refined into simple multi-domain architectures using a recently developed in-house algorithm, DomainFinder 3 (available at: ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/DomainFinder3/). The domain assignments are integrated with multiple external protein function descriptions (e.g. Gene Ontology and KEGG), structural annotations (e.g. coiled coils, disordered regions and sequence polymorphisms) and family resources (e.g. Pfam and eggNog) and displayed on the Gene3D website. The website allows users to view descriptions for both single proteins and genes and large protein sets, such as superfamilies or genomes. Subsets can then be selected for detailed investigation or associated functions and interactions can be used to expand explorations to new proteins. Gene3D also provides a set of services, including an interactive genome coverage graph visualizer, DAS annotation resources, sequence search facilities and SOAP services.

Investigation of Domain Structure in (001) PMN-x%PT Crystals by Scanning Force Microscope

The domain structures of annealed (001)-oriented <TEX>$Pb(Mg_{1/3}Nb_{2/3})O_3-x%PbTiO_3$</TEX> (PMN-x%PT) crystals for x = 10, 20, 30, 35, and 40 at% were investigated by Polarized Optical Microscopy (POM) and Scanning Force Microscopy (SFM) in the piezoresponse mode. Both Polar Nano-Domains (PND) and long strip-like domains were clearly observed. The results also showed how the domain structure changed between phases with an increasing x in the PMN-x%PT crystals and the domain hierarchy on various length scales ranging from 40 nm to 0.1 mm. Distorted pseudo-cubic phase (x < 20%) consisted of PNDs that did not self-assemble into macro-domain plates. The rhombohedral phase (x = 30%) consisted of PNDs that began to self-assemble into colonies along preferred {110} planes. The monoclinic phase (x = 35%) consisted of miniature polar domains on the nm scale, whereas, the tetragonal phase (x = 40%) consisted of {001} oriented lamella domains on the mm scale that had internal nano-scale heterogeneities, which self-assembled into macro-domain plates oriented along {001} the mm scale.

Growth of fat slits and dispersionless KP hierarchy

A ‘fat slit’ is a compact domain in the upper half-plane bounded by a curve with endpoints on the real axis and a segment of the real axis between them. We consider conformal maps of the upper half-plane to the exterior of a fat slit parameterized by harmonic moments of the latter and show that they obey an infinite set of Lax equations for the dispersionless KP hierarchy. Deformation of a fat slit under changing a particular harmonic moment can be treated as a growth process similar to the Laplacian growth of domains in the whole plane. This construction extends the well-known link between solutions to the dispersionless KP hierarchy and conformal maps of slit domains in the upper half-plane and provides a new, large family of solutions.

Domain Hierarchy and closed Loops (DHcL): a server for exploring hierarchy of protein domain structure

Domain hierarchy and closed loops (DHcL) (http://sitron.bccs.uib.no/dhcl/) is a web server that delineates energy hierarchy of protein domain structure and detects domains at different levels of this hierarchy. The server also identifies closed loops and van der Waals locks, which constitute a structural basis for the protein domain hierarchy. The DHcL can be a useful tool for an express analysis of protein structures and their alternative domain decompositions. The user submits a PDB identifier(s) or uploads a 3D protein structure in a PDB format. The results of the analysis are the location of domains at different levels of hierarchy, closed loops, van der Waals locks and their interactive visualization. The server maintains a regularly updated database of domains, closed loop and van der Waals locks for all X-ray structures in PDB. DHcL server is available at: http://sitron.bccs.uib.no/dhcl.