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John-Marc Chandonia

Publications and source records attributed to John-Marc Chandonia.

11 recordsLinked to original sources
PubMed2006

Structural proteomics of minimal organisms: conservation of protein fold usage and evolutionary implications.

BACKGROUND: Determining the complete repertoire of protein structures for all soluble, globular proteins in a single organism has been one of the major goals of several structural genomics projects in recent years. RESULTS: We report that this goal has nearly been reached for several "minimal organisms"--parasites or symbionts with reduced genomes--for which over 95% of the soluble, globular proteins may now be assigned folds, overall 3-D backbone structures. We analyze the structures of these proteins as they relate to cellular functions, and compare conservation of fold usage between functional categories. We also compare patterns in the conservation of folds among minimal organisms and those observed between minimal organisms and other bacteria. CONCLUSION: We find that proteins performing essential cellular functions closely related to transcription and translation exhibit a higher degree of conservation in fold usage than proteins in other functional categories. Folds related to transcription and translation functional categories were also overrepresented in minimal organisms compared to other bacteria.

Bacterial Proteins↗
PubMed2006

Target selection and deselection at the Berkeley Structural Genomics Center.

At the Berkeley Structural Genomics Center (BSGC), our goal is to obtain a near-complete structural complement of proteins in the minimal organisms Mycoplasma genitalium and M. pneumoniae, two closely related pathogens. Current targets for structure determination have been selected in six major stages, starting with those predicted to be most tractable to high throughput study and likely to yield new structural information. We report on the process used to select these proteins, as well as our target deselection procedure. Target deselection reduces experimental effort by eliminating targets similar to those recently solved by the structural biology community or other centers. We measure the impact of the 69 structures solved at the BSGC as of July 2004 on structure prediction coverage of the M. pneumoniae and M. genitalium proteomes. The number of Mycoplasma proteins for which the fold could first be reliably assigned based on structures solved at the BSGC (24 M. pneumoniae and 21 M. genitalium) is approximately 25% of the total resulting from work at all structural genomics centers and the worldwide structural biology community (94 M. pneumoniae and 86 M. genitalium) during the same period. As the number of structures contributed by the BSGC during that period is less than 1% of the total worldwide output, the benefits of a focused target selection strategy are apparent. If the structures of all current targets were solved, the percentage of M. pneumoniae proteins for which folds could be reliably assigned would increase from approximately 57% (391 of 687) at present to around 80% (550 of 687), and the percentage of the proteome that could be accurately modeled would increase from around 37% (254 of 687) to about 64% (438 of 687). In M. genitalium, the percentage of the proteome that could be structurally annotated based on structures of our remaining targets would rise from 72% (348 of 486) to around 76% (371 of 486), with the percentage of accurately modeled proteins would rise from 50% (243 of 486) to 58% (283 of 486). Sequences and data on experimental progress on our targets are available in the public databases TargetDB and PEPCdb.

Amino Acids↗
PubMed2006

The impact of structural genomics: expectations and outcomes.

Structural genomics (SG) projects aim to expand our structural knowledge of biological macromolecules while lowering the average costs of structure determination. We quantitatively analyzed the novelty, cost, and impact of structures solved by SG centers, and we contrast these results with traditional structural biology. The first structure identified in a protein family enables inference of the fold and of ancient relationships to other proteins; in the year ending 31 January 2005, about half of such structures were solved at a SG center rather than in a traditional laboratory. Furthermore, the cost of solving a structure at the most efficient SG center in the United States has dropped to one-quarter of the estimated cost of solving a structure by traditional methods. However, the efficiency of the top structural biology laboratories-even though they work on very challenging structures-is comparable to that of SG centers; moreover, traditional structural biology papers are cited significantly more often, suggesting greater current impact.

Amino Acid Sequence↗
PubMed2006

ANDY: a general, fault-tolerant tool for database searching on computer clusters.

SUMMARY: ANDY (seArch coordination aND analYsis) is a set of Perl programs and modules for distributing large biological database searches, and in general any sequence of commands, across the nodes of a Linux computer cluster. ANDY is compatible with several commonly used distributed resource management (DRM) systems, and it can be easily extended to new DRMs. A distinctive feature of ANDY is the choice of either dedicated or fair-use operation: ANDY is almost as efficient as single-purpose tools that require a dedicated cluster, but it runs on a general-purpose cluster along with any other jobs scheduled by a DRM. Other features include communication through named pipes for performance, flexible customizable routines for error-checking and summarizing results, and multiple fault-tolerance mechanisms. AVAILABILITY: ANDY is freely available and can be obtained from http://compbio.berkeley.edu/proj/andy. SUPPLEMENTARY INFORMATION: Supplemental data, figures, and a more detailed overview of the software are found at http://compbio.berkeley.edu/proj/andy.

Computing Methodologies↗
PubMed2005

Comparative mapping of sequence-based and structure-based protein domains.

BACKGROUND: Protein domains have long been an ill-defined concept in biology. They are generally described as autonomous folding units with evolutionary and functional independence. Both structure-based and sequence-based domain definitions have been widely used. But whether these types of models alone can capture all essential features of domains is still an open question. METHODS: Here we provide insight on domain definitions through comparative mapping of two domain classification databases, one sequence-based (Pfam) and the other structure-based (SCOP). A mapping score is defined to indicate the significance of the mapping, and the properties of the mapping matrices are studied. RESULTS: The mapping results show a general agreement between the two databases, as well as many interesting areas of disagreement. In the cases of disagreement, the functional and evolutionary characteristics of the domains are examined to determine which domain definition is biologically more informative.

Algorithms↗
PubMed2005

Implications of structural genomics target selection strategies: Pfam5000, whole genome, and random approaches.

Structural genomics is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy that is medically and biologically relevant, of good value, and tractable. As an option to consider, we present the "Pfam5000" strategy, which involves selecting the 5000 most important families from the Pfam database as sources for targets. We compare the Pfam5000 strategy to several other proposed strategies that would require similar numbers of targets. These strategies include complete solution of several small to moderately sized bacterial proteomes, partial coverage of the human proteome, and random selection of approximately 5000 targets from sequenced genomes. We measure the impact that successful implementation of these strategies would have upon structural interpretation of the proteins in Swiss-Prot, TrEMBL, and 131 complete proteomes (including 10 of eukaryotes) from the Proteome Analysis database at the European Bioinformatics Institute (EBI). Solving the structures of proteins from the 5000 largest Pfam families would allow accurate fold assignment for approximately 68% of all prokaryotic proteins (covering 59% of residues) and 61% of eukaryotic proteins (40% of residues). More fine-grained coverage that would allow accurate modeling of these proteins would require an order of magnitude more targets. The Pfam5000 strategy may be modified in several ways, for example, to focus on larger families, bacterial sequences, or eukaryotic sequences; as long as secondary consideration is given to large families within Pfam, coverage results vary only slightly. In contrast, focusing structural genomics on a single tractable genome would have only a limited impact in structural knowledge of other proteomes: A significant fraction (about 30-40% of the proteins and 40-60% of the residues) of each proteome is classified in small families, which may have little overlap with other species of interest. Random selection of targets from one or more genomes is similar to the Pfam5000 strategy in that proteins from larger families are more likely to be chosen, but substantial effort would be spent on small families.

Animals↗
PubMed2005

Structural genomics of minimal organisms and protein fold space.

The initial aim of the Berkeley Structural Genomics Center is to obtain a near-complete structural complement of two minimal organisms, closely related pathogens Mycoplasma genitalium and M. pneumoniae. The former has fewer than 500 genes and the latter fewer than 700 genes. To achieve this goal, the current protein targets have been selected starting with those predicted to be most tractable and likely to yield new structural and functional information. During the past 3 years, the semi-automated structural genomics pipeline has been set up from cloning, expression, purification, and ultimately to structural determination. The results from the pipeline substantially increased the coverage of the protein fold space of M. pneumoniae and M. genitalium. Furthermore, about 1/2 of the structures of 'unique' protein sequences revealed new and novel folds, and over 2/3 of the structures of previously annotated 'hypothetical proteins' inferred their molecular functions.

Bacterial Proteins↗
PubMed2004

The ASTRAL Compendium in 2004.

The ASTRAL Compendium provides several databases and tools to aid in the analysis of protein structures, particularly through the use of their sequences. Partially derived from the SCOP database of protein structure domains, it includes sequences for each domain and other resources useful for studying these sequences and domain structures. The current release of ASTRAL contains 54,745 domains, more than three times as many as the initial release 4 years ago. ASTRAL has undergone major transformations in the past 2 years. In addition to several complete updates each year, ASTRAL is now updated on a weekly basis with preliminary classifications of domains from newly released PDB structures. These classifications are available as a stand-alone database, as well as integrated into other ASTRAL databases such as representative subsets. To enhance the utility of ASTRAL to structural biologists, all SCOP domains are now made available as PDB-style coordinate files as well as sequences. In addition to sequences and representative subsets based on SCOP domains, sequences and subsets based on PDB chains are newly included in ASTRAL. Several search tools have been added to ASTRAL to facilitate retrieval of data by individual users and automated methods. ASTRAL may be accessed at http://astral.stanford. edu/.

Animals↗
PubMed2004

WebLogo: a sequence logo generator.

WebLogo generates sequence logos, graphical representations of the patterns within a multiple sequence alignment. Sequence logos provide a richer and more precise description of sequence similarity than consensus sequences and can rapidly reveal significant features of the alignment otherwise difficult to perceive. Each logo consists of stacks of letters, one stack for each position in the sequence. The overall height of each stack indicates the sequence conservation at that position (measured in bits), whereas the height of symbols within the stack reflects the relative frequency of the corresponding amino or nucleic acid at that position. WebLogo has been enhanced recently with additional features and options, to provide a convenient and highly configurable sequence logo generator. A command line interface and the complete, open WebLogo source code are available for local installation and customization.

Amino Acid Sequence↗
PubMed2002

ASTRAL compendium enhancements.

The ASTRAL compendium provides several databases and tools to aid in the analysis of protein structures, particularly through the use of their sequences. It is partially derived from the SCOP database of protein domains, and it includes sequences for each domain as well as other resources useful for studying these sequences and domain structures. Several major improvements have been made to the ASTRAL compendium since its initial release 2 years ago. The number of protein domain sequences included has doubled from 15 190 to 30 867, and additional databases have been added. The Rapid Access Format (RAF) database contains manually curated mappings linking the biological amino acid sequences described in the SEQRES records of PDB entries to the amino acid sequences structurally observed (provided in the ATOM records) in a format designed for rapid access by automated tools. This information is used to derive sequences for protein domains in the SCOP database. In cases where a SCOP domain spans several protein chains, all of which can be traced back to a single genetic source, a 'genetic domain' sequence is created by concatenating the sequences of each chain in the order found in the original gene sequence. Both the original-style library of SCOP sequences and a new library including genetic domain sequences are available. Selected representative subsets of each of these libraries, based on multiple criteria and degrees of similarity, are also included. ASTRAL may be accessed at http://astral.stanford.edu/.

Amino Acid Sequence↗