Biomedical subjects

Domenico Cozzetto

Publications and source records attributed to Domenico Cozzetto.

4 recordsLinked to original sources

PubMed2006

An analysis of the Sargasso Sea resource and the consequences for database composition.

BACKGROUND: The environmental sequencing of the Sargasso Sea has introduced a huge new resource of genomic information. Unlike the protein sequences held in the current searchable databases, the Sargasso Sea sequences originate from a single marine environment and have been sequenced from species that are not easily obtainable by laboratory cultivation. The resource also contains very many fragments of whole protein sequences, a side effect of the shotgun sequencing method.These sequences form a significant addendum to the current searchable databases but also present us with some intrinsic difficulties. While it is important to know whether it is possible to assign function to these sequences with the current methods and whether they will increase our capacity to explore sequence space, it is also interesting to know how current bioinformatics techniques will deal with the new sequences in the resource. RESULTS: The Sargasso Sea sequences seem to introduce a bias that decreases the potential of current methods to propose structure and function for new proteins. In particular the high proportion of sequence fragments in the resource seems to result in poor quality multiple alignments. CONCLUSION: These observations suggest that the new sequences should be used with care, especially if the information is to be used in large scale analyses. On a positive note, the results may just spark improvements in computational and experimental methods to take into account the fragments generated by environmental sequencing techniques.

Amino Acid Sequence↗

PubMed2006

The PMDB Protein Model Database.

The Protein Model Database (PMDB) is a public resource aimed at storing manually built 3D models of proteins. The database is designed to provide access to models published in the scientific literature, together with validating experimental data. It is a relational database and it currently contains >74,000 models for approximately 240 proteins. The system is accessible at http://www.caspur.it/PMDB and allows predictors to submit models along with related supporting evidence and users to download them through a simple and intuitive interface. Users can navigate in the database and retrieve models referring to the same target protein or to different regions of the same protein. Each model is assigned a unique identifier that allows interested users to directly access the data.

Databases, Protein↗

PubMed2005

Relationship between multiple sequence alignments and quality of protein comparative models.

Comparative modeling is the method of choice, whenever applicable, for protein structure prediction, not only because of its higher accuracy compared to alternative methods, but also because it is possible to estimate a priori the quality of the models that it can produce, thereby allowing the usefulness of a model for a given application to be assessed beforehand. By and large, the quality of a comparative model depends on two factors: the extent of structural divergence between the target and the template and the quality of the sequence alignment between the two protein sequences. The latter is usually derived from a multiple sequence alignment (MSA) of as many proteins of the family as possible, and its accuracy depends on the number and similarity distribution of the sequences of the protein family. Here we describe a method to evaluate the expected difficulty, and by extension accuracy, of a comparative model on the basis of the MSA used to build it. The parameter that we derive is used to compare the results obtained in the last two editions of the Critical Assessment of Methods for Structure Prediction (CASP) experiment as a function of the difficulty of the modeling exercise. Our analysis demonstrates that the improvement in the scope and quality of comparative models between the two experiments is largely due to the increased number of available protein sequences and to the consequent increased chance that a large and appropriately spaced set of protein sequences homologous to the proteins of interest is available.

Amino Acid Sequence↗

PubMed2005

Ten years of predictions ... and counting.

The CASP experiment has been run every other year since 1994. Its objective is to subject the available structure prediction methods to a blind test. This is a short report of the highlights of its last edition. 'Men who wish to know about the world must learn about it in its particular details' (Heraclitus of Ephesus, 535-475 bc).

Computational Biology↗