NBLAST: a cluster variant of BLAST for NxN comparisons

Background  

The BLAST algorithm compares biological sequences to one another in order to determine shared motifs and common ancestry. However, the comparison of all non-redundant (NR) sequences against all other NR sequences is a computationally intensive task. We developed NBLAST as a cluster computer implementation of the BLAST family of sequence comparison programs for the purpose of generating pre-computed BLAST alignments and neighbour lists of NR sequences.     

PreBIND and Textomy – mining the biomedical literature for protein-protein interactions using a support vector machine

Background

The majority of experimentally verified molecular interaction and biological pathway data are present in the unstructured text of biomedical journal articles where they are inaccessible to computational methods. The Biomolecular interaction network database (BIND) seeks to capture these data in a machine-readable format. We hypothesized that the formidable task-size of backfilling the database could be reduced by using Support Vector Machine technology to first locate interaction information in the literature. We present an information extraction system that was designed to locate protein-protein interaction data in the literature and present these data to curators and the public for review and entry into BIND.

Results

Cross-validation estimated the support vector machine's test-set precision, accuracy and recall for classifying abstracts describing interaction information was 92%, 90% and 92% respectively. We estimated that the system would be able to recall up to 60% of all non-high throughput interactions present in another yeast-protein interaction database. Finally, this system was applied to a real-world curation problem and its use was found to reduce the task duration by 70% thus saving 176 days.

Conclusions

Machine learning methods are useful as tools to direct interaction and pathway database back-filling; however, this potential can only be realized if these techniques are coupled with human review and entry into a factual database such as BIND. The PreBIND system described here is available to the public at http://bind.ca. Current capabilities allow searching for human, mouse and yeast protein-interaction information.     

An automated method for finding molecular complexes in large protein interaction networks

Background  

Recent advances in proteomics technologies such as two-hybrid, phage display and mass spectrometry have enabled us to create a detailed map of biomolecular interaction networks. Initial mapping efforts have already produced a wealth of data. As the size of the interaction set increases, databases and computational methods will be required to store, visualize and analyze the information in order to effectively aid in knowledge discovery.     

Domain-based small molecule binding site annotation

Background  

Accurate small molecule binding site information for a protein can facilitate studies in drug docking, drug discovery and function prediction, but small molecule binding site protein sequence annotation is sparse. The Small Molecule Interaction Database (SMID), a database of protein domain-small molecule interactions, was created using structural data from the Protein Data Bank (PDB). More importantly it provides a means to predict small molecule binding sites on proteins with a known or unknown structure and unlike prior approaches, removes large numbers of false positive hits arising from transitive alignment errors, non-biologically significant small molecules and crystallographic conditions that overpredict ion binding sites.     

The Effects of Calcium and the Ionophore A23I87 on Modulation, Nitrogen Fixation and Growth of Soybeans

Tryptophan synthase in Phycomyces blakesleeanus. Part II: Activity of tryptophan synthase in Phycomyces blakesleeanus depending on the light and the content of zinc ions in the culture medium Five-day-old cultures of Phycomyces blakesleeanus show notice-able differences in the phenotype, depending on the culture conditions (permanent light, permanent dark, zinc deficiency, zinc sufficiency) and related to the distribution of tryptophan synthase activity between mycelium and sporangiophores. Permanent light and the presence of zinc ions in the medium during culturing have an antagonistic influence on the tryptophan synthase. The activity of the enzyme is being reduced in the sporangiophores and increased in the mycelium by the influence of light, while zinc ions in the culture medium increase the activity in the sporangiophores at simultaneous reduction in the mycelium. The importance of tryptophan synthase and tryptophan for the development of the fungus in relation to the metabolism of indole acetic acid is discussed.     

Prevention of aluminium toxicity with supplemental boron. II. Stimulation of root growth in an acidic, high-aluminium subsoil

Root growth inhibition is an early symptom of Al toxicity and B deficiency. Our hypothesis is that Al toxicity may induce B deficiency, and it was our objective to determine if incorporation of supplemental B would promote root penetration into an acidic, high-Al subsoil. Alfalfa (Medicago sativa L. cv. Hy-Phy) was grown in slanted tubes with a Plexiglas window along their length. The top half of the tub contained silt loam soil and the bottom half contained subsoil from the Bt1 horizon (26% Al saturation) of a Creldon silty clay loam. Both soils originally contained 0–9 kg B ha^?1. When root growth was measured in the bottom half of the high-A1 subsoil, all measurements—depth of rooting, total root growth, final root lengths and root dry weight—demonstrated greater root growth in treatments where additional B was incorporated into the high-Al subsoil. Results from this soil study extend those obtained in our hydroponic study in which supplemental B presented Al inhibition of root growth. Boron concentrations may need to he increased under acidic ‘high-Al’ soil conditions to promote root penetration into these soil zones, and this could be especially important during periods of drought stress.     

Microhabitat use by white-footed mice Peromyscus leucopus in forested and old-field habitats occupied by Morrow's honeysuckle Lonicera morrowii

We quantified microhabitat use by white-footed mice Peromyscus leucopus in forest and old-field habitats occupied by Morrow's honeysuckle Lonicera morrowii, an invasive exotic shrub imported from Japan. Microhabitat characteristics were compared between trails used by mice (n=124) and randomly selected trails (n=127) in 4 study plots located at Fort Necessity National Battlefield, Farmington, Pennsylvania, USA. We compared 10 microhabitat variables between used and random trails using non-metric multidimensional scaling (NMDS) and classification and regression tree (CART) analysis. Trails used by mice were statistically different from randomly selected trails in both forested plots (P<0.008) and old-field plots (P<0.001). In the forested plots, trails of white-footed mice were more often associated with a greater percent cover (% cover) of coarse woody debris (CWD) than were randomly selected trails. In the old-field plots, mouse trails were commonly characterized by having a lower % cover of exotic herbaceous vegetation, a greater % cover of shrubs, and a greater % cover of Morrow's honeysuckle than randomly selected trails. Our study indicates that white-footed mice do not move randomly and prefer areas of high structural complexity, thereby showing significant microhabitat preference. The preference of white-footed mice for areas with a relatively high percent cover of Morrow's honeysuckle could 1) be a factor in the aggressive nature of the exotic honeysuckle shrub's spread throughout the Battlefield or 2) cause the shrub to spread even faster into adjacent areas not yet occupied by Morrow's honeysuckle[Current Zoology 55(2):111-122,2009].     

Species-specific protein sequence and fold optimizations

Background

An organism's ability to adapt to its particular environmental niche is of fundamental importance to its survival and proliferation. In the largest study of its kind, we sought to identify and exploit the amino-acid signatures that make species-specific protein adaptation possible across 100 complete genomes.

Results

Environmental niche was determined to be a significant factor in variability from correspondence analysis using the amino acid composition of over 360,000 predicted open reading frames (ORFs) from 17 archae, 76 bacteria and 7 eukaryote complete genomes. Additionally, we found clusters of phylogenetically unrelated archae and bacteria that share similar environments by amino acid composition clustering. Composition analyses of conservative, domain-based homology modeling suggested an enrichment of small hydrophobic residues Ala, Gly, Val and charged residues Asp, Glu, His and Arg across all genomes. However, larger aromatic residues Phe, Trp and Tyr are reduced in folds, and these results were not affected by low complexity biases. We derived two simple log-odds scoring functions from ORFs (C_G) and folds (C_F) for each of the complete genomes. C_F achieved an average cross-validation success rate of 85 ± 8% whereas the C_G detected 73 ± 9% species-specific sequences when competing against all other non-redundant C_G. Continuously updated results are available at http://genome.mshri.on.ca.

Conclusion

Our analysis of amino acid compositions from the complete genomes provides stronger evidence for species-specific and environmental residue preferences in genomic sequences as well as in folds. Scoring functions derived from this work will be useful in future protein engineering experiments and possibly in identifying horizontal transfer events.