Genomic structure and marker-derived gene networks for growth and meat quality traits of Brazilian Nelore beef cattle.

BACKGROUND: Nelore is the major beef cattle breed in Brazil with more than 130 million heads. Genome-wide association studies (GWAS) are often used to associate markers and genomic regions to growth and meat quality traits that can be used to assist selection programs. An alternative methodology to traditional GWAS that involves the construction of gene network interactions, derived from results of several GWAS is the AWM (Association Weight Matrices)/PCIT (Partial Correlation and Information Theory). With the aim of evaluating the genetic architecture of Brazilian Nelore cattle, we used high-density SNP genotyping data (~770,000 SNP) from 780 Nelore animals comprising 34 half-sibling families derived from highly disseminated and unrelated sires from across Brazil. The AWM/PCIT methodology was employed to evaluate the genes that participate in a series of eight phenotypes related to growth and meat quality obtained from this Nelore sample. RESULTS: Our results indicate a lack of structuring between the individuals studied since principal component analyses were not able to differentiate families by its sires or by its ancestral lineages. The application of the AWM/PCIT methodology revealed a trio of transcription factors (comprising VDR, LHX9 and ZEB1) which in combination connected 66 genes through 359 edges and whose biological functions were inspected, some revealing to participate in biological growth processes in literature searches. CONCLUSIONS: The diversity of the Nelore sample studied is not high enough to differentiate among families neither by sires nor by using the available ancestral lineage information. The gene networks constructed from the AWM/PCIT methodology were a useful alternative in characterizing genes and gene networks that were allegedly influential in growth and meat quality traits in Nelore cattle.

Genome-wide association for growth traits in Canchim beef cattle.

Studies are being conducted on the applicability of genomic data to improve the accuracy of the selection process in livestock, and genome-wide association studies (GWAS) provide valuable information to enhance the understanding on the genetics of complex traits. The aim of this study was to identify genomic regions and genes that play roles in birth weight (BW), weaning weight adjusted for 210 days of age (WW), and long-yearling weight adjusted for 420 days of age (LYW) in Canchim cattle. GWAS were performed by means of the Generalized Quasi-Likelihood Score (GQLS) method using genotypes from the BovineHD BeadChip and estimated breeding values for BW, WW, and LYW. Data consisted of 285 animals from the Canchim breed and 114 from the MA genetic group (derived from crossings between Charolais sires and ½ Canchim + ½ Zebu dams). After applying a false discovery rate correction at a 10% significance level, a total of 4, 12, and 10 SNPs were significantly associated with BW, WW, and LYW, respectively. These SNPs were surveyed to their corresponding genes or to surrounding genes within a distance of 250 kb. The genes DPP6 (dipeptidyl-peptidase 6) and CLEC3B (C-type lectin domain family 3 member B) were highlighted, considering its functions on the development of the brain and skeletal system, respectively. The GQLS method identified regions on chromosome associated with birth weight, weaning weight, and long-yearling weight in Canchim and MA animals. New candidate regions for body weight traits were detected and some of them have interesting biological functions, of which most have not been previously reported. The observation of QTL reports for body weight traits, covering areas surrounding the genes (SNPs) herein identified provides more evidence for these associations. Future studies targeting these areas could provide further knowledge to uncover the genetic architecture underlying growth traits in Canchim cattle.

PDB-Metrics: a web tool for exploring the PDB contents.

PDB-Metrics (http://sms.cbi.cnptia.embrapa.br/SMS/pdb_metrics/index.html) is a component of the Diamond STING suite of programs for the analysis of protein sequence, structure and function. It summarizes the characteristics of the collection of protein structure descriptions deposited in the Protein Data Bank (PDB) and provides a Web interface to search and browse the PDB, using a variety of alternative criteria. PDB-Metrics is a powerful tool for bioinformaticians to examine the data span in the PDB from several perspectives. Although other Web sites offer some similar resources to explore the PDB contents, PDB-Metrics is among those with the most complete set of such facilities, integrated into a single Web site. This program has been developed using SQLite, a C library that provides all the query facilities of a database management system.

Predicting enzyme class from protein structure using Bayesian classification.

Predicting enzyme class from protein structure parameters is a challenging problem in protein analysis. We developed a method to predict enzyme class that combines the strengths of statistical and data-mining methods. This method has a strong mathematical foundation and is simple to implement, achieving an accuracy of 45%. A comparison with the methods found in the literature designed to predict enzyme class showed that our method outperforms the existing methods.

The Diamond STING server.

Diamond STING is a new version of the STING suite of programs for a comprehensive analysis of a relationship between protein sequence, structure, function and stability. We have added a number of new functionalities by both providing more structure parameters to the STING Database and by improving/expanding the interface for enhanced data handling. The integration among the STING components has also been improved. A new key feature is the ability of the STING server to handle local files containing protein structures (either modeled or not yet deposited to the Protein Data Bank) so that they can be used by the principal STING components: (Java)Protein Dossier ((J)PD) and STING Report. The current capabilities of the new STING version and a couple of biologically relevant applications are described here. We have provided an example where Diamond STING identifies the active site amino acids and folding essential amino acids (both previously determined by experiments) by filtering out all but those residues by selecting the numerical values/ranges for a set of corresponding parameters. This is the fundamental step toward a more interesting endeavor-the prediction of such residues. Diamond STING is freely accessible at http://sms.cbi.cnptia.embrapa.br and http://trantor.bioc.columbia.edu/SMS.

STING Report: convenient web-based application for graphic and tabular presentations of protein sequence, structure and function descriptors from the STING database.

The Sting Report is a versatile web-based application for extraction and presentation of detailed information about any individual amino acid of a protein structure stored in the STING Database. The extracted information is presented as a series of GIF images and tables, containing the values of up to 125 sequence/structure/function descriptors/parameters. The GIF images are generated by the Gold STING modules. The HTML page resulting from the STING Report query can be printed and, most importantly, it can be composed and visualized on a computer platform with an elementary configuration. Using the STING Report, a user can generate a collection of customized reports for amino acids of specific interest. Such a collection comes as an ideal match for a demand for the rapid and detailed consultation and documentation of data about structure/function. The inclusion of information generated with STING Report in a research report or even a textbook, allows for the increased density of its contents. STING Report is freely accessible within the Gold STING Suite at http://www.cbi.cnptia.embrapa.br, http://www.es.embnet.org/SMS/, http://gibk26.bse.kyutech.ac.jp/SMS/ and http://trantor.bioc.columbia.edu/SMS (option: STING Report).

STING Millennium Suite: integrated software for extensive analyses of 3d structures of proteins and their complexes.

BACKGROUND: The integration of many aspects of protein/DNA structure analysis is an important requirement for software products in general area of structural bioinformatics. In fact, there are too few software packages on the internet which can be described as successful in this respect. We might say that what is still missing is publicly available, web based software for interactive analysis of the sequence/structure/function of proteins and their complexes with DNA and ligands. Some of existing software packages do have certain level of integration and do offer analysis of several structure related parameters, however not to the extent generally demanded by a user. RESULTS: We are reporting here about new Sting Millennium Suite (SMS) version which is fully accessible (including for local files at client end), web based software for molecular structure and sequence/structure/function analysis. The new SMS client version is now operational also on Linux boxes and it works with non-public pdb formatted files (structures not deposited at the RCSB/PDB), eliminating earlier requirement for the registration if SMS components were to be used with user's local files. At the same time the new SMS offers some important additions and improvements such as link to ProTherm as well as significant re-engineering of SMS component ConSSeq. Also, we have added 3 new SMS mirror sites to existing network of global SMS servers: Argentina, Japan and Spain. CONCLUSION: SMS is already established software package and many key data base and software servers worldwide, do offer either a link to, or host the SMS. SMS (Sting Millennium Suite) is web-based publicly available software developed to aid researches in their quest for translating information about the structures of macromolecules into knowledge. SMS allows to a user to interactively analyze molecular structures, cross-referencing visualized information with a correlated one, available across the internet. SMS is already used as a didactic tool by some universities. SMS analysis is now possible on Linux OS boxes and with no requirement for registration when using local files.

JavaProtein Dossier: a novel web-based data visualization tool for comprehensive analysis of protein structure.

JavaProtein Dossier ((J)PD) is a new concept, database and visualization tool providing one of the largest collections of the physicochemical parameters describing proteins' structure, stability, function and interaction with other macromolecules. By collecting as many descriptors/parameters as possible within a single database, we can achieve a better use of the available data and information. Furthermore, data grouping allows us to generate different parameters with the potential to provide new insights into the sequence-structure-function relationship. In (J)PD, residue selection can be performed according to multiple criteria. (J)PD can simultaneously display and analyze all the physicochemical parameters of any pair of structures, using precalculated structural alignments, allowing direct parameter comparison at corresponding amino acid positions among homologous structures. In order to focus on the physicochemical (and consequently pharmacological) profile of proteins, visualization tools (showing the structure and structural parameters) also had to be optimized. Our response to this challenge was the use of Java technology with its exceptional level of interactivity. (J)PD is freely accessible (within the Gold Sting Suite) at http://sms.cbi.cnptia.embrapa.br, http://mirrors.rcsb.org/SMS, http://trantor.bioc.columbia.edu/SMS and http://www.es.embnet.org/SMS/ (Option: (Java)Protein Dossier).

STING Millennium: A web-based suite of programs for comprehensive and simultaneous analysis of protein structure and sequence.

STING Millennium Suite (SMS) is a new web-based suite of programs and databases providing visualization and a complex analysis of molecular sequence and structure for the data deposited at the Protein Data Bank (PDB). SMS operates with a collection of both publicly available data (PDB, HSSP, Prosite) and its own data (contacts, interface contacts, surface accessibility). Biologists find SMS useful because it provides a variety of algorithms and validated data, wrapped-up in a user friendly web interface. Using SMS it is now possible to analyze sequence to structure relationships, the quality of the structure, nature and volume of atomic contacts of intra and inter chain type, relative conservation of amino acids at the specific sequence position based on multiple sequence alignment, indications of folding essential residue (FER) based on the relationship of the residue conservation to the intra-chain contacts and Calpha-Calpha and Cbeta-Cbeta distance geometry. Specific emphasis in SMS is given to interface forming residues (IFR)-amino acids that define the interactive portion of the protein surfaces. SMS may simultaneously display and analyze previously superimposed structures. PDB updates trigger SMS updates in a synchronized fashion. SMS is freely accessible for public data at http://www.cbi.cnptia.embrapa.br, http://mirrors.rcsb.org/SMS and http://trantor.bioc.columbia.edu/SMS.