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P Bertone

Publications and source records attributed to P Bertone.

9 recordsLinked to original sources

GeneCensus: genome comparisons in terms of metabolic pathway activity and protein family sharing.

We present a prototype of a new database tool, GeneCensus, which focuses on comparing genomes globally, in terms of the collective properties of many genes, rather than in terms of the attributes of a single gene (e.g. sequence similarity for a particular ortholog). The comparisons are presented in a visual fashion over the web at GeneCensus.org. The system concentrates on two types of comparisons: (i) trees based on the sharing of generalized protein families between genomes, and (ii) whole pathway analysis in terms of activity levels. For the trees, we have developed a module (TreeViewer) that clusters genomes in terms of the folds, superfamilies or orthologs--all can be considered as generalized 'families' or 'protein parts'--they share, and compares the resulting trees side-by-side with those built from sequence similarity of individual genes (e.g. a traditional tree built on ribosomal similarity). We also include comparisons to trees built on whole-genome dinucleotide or codon composition. For pathway comparisons, we have implemented a module (PathwayPainter) that graphically depicts, in selected metabolic pathways, the fluxes or expression levels of the associated enzymes (i.e. generalized 'activities'). One can, consequently, compare organisms (and organism states) in terms of representations of these systemic quantities. Develop ment of this module involved compiling, calculating and standardizing flux and expression information from many different sources. We illustrate pathway analysis for enzymes involved in central metabolism. We are able to show that, to some degree, flux and expression fluctuations have characteristic values in different sections of the central metabolism and that control points in this system (e.g. hexokinase, pyruvate kinase, phosphofructokinase, isocitrate dehydrogenase and citric synthase) tend to be especially variable in flux and expression. Both the TreeViewer and PathwayPainter modules connect to other information sources related to individual-gene or organism properties (e.g. a single-gene structural annotation viewer).

Animals↗

Global analysis of protein activities using proteome chips.

To facilitate studies of the yeast proteome, we cloned 5800 open reading frames and overexpressed and purified their corresponding proteins. The proteins were printed onto slides at high spatial density to form a yeast proteome microarray and screened for their ability to interact with proteins and phospholipids. We identified many new calmodulin- and phospholipid-interacting proteins; a common potential binding motif was identified for many of the calmodulin-binding proteins. Thus, microarrays of an entire eukaryotic proteome can be prepared and screened for diverse biochemical activities. The microarrays can also be used to screen protein-drug interactions and to detect posttranslational modifications.

Amino Acid Motifs↗

SPINE: an integrated tracking database and data mining approach for identifying feasible targets in high-throughput structural proteomics.

High-throughput structural proteomics is expected to generate considerable amounts of data on the progress of structure determination for many proteins. For each protein this includes information about cloning, expression, purification, biophysical characterization and structure determination via NMR spectroscopy or X-ray crystallography. It will be essential to develop specifications and ontologies for standardizing this information to make it amenable to retrospective analysis. To this end we created the SPINE database and analysis system for the Northeast Structural Genomics Consortium. SPINE, which is available at bioinfo.mbb.yale.edu/nesg or nesg.org, is specifically designed to enable distributed scientific collaboration via the Internet. It was designed not just as an information repository but as an active vehicle to standardize proteomics data in a form that would enable systematic data mining. The system features an intuitive user interface for interactive retrieval and modification of expression construct data, query forms designed to track global project progress and external links to many other resources. Currently the database contains experimental data on 985 constructs, of which 740 are drawn from Methanobacterium thermoautotrophicum, 123 from Saccharomyces cerevisiae, 93 from Caenorhabditis elegans and the remainder from other organisms. We developed a comprehensive set of data mining features for each protein, including several related to experimental progress (e.g. expression level, solubility and crystallization) and 42 based on the underlying protein sequence (e.g. amino acid composition, secondary structure and occurrence of low complexity regions). We demonstrate in detail the application of a particular machine learning approach, decision trees, to the tasks of predicting a protein's solubility and propensity to crystallize based on sequence features. We are able to extract a number of key rules from our trees, in particular that soluble proteins tend to have significantly more acidic residues and fewer hydrophobic stretches than insoluble ones. One of the characteristics of proteomics data sets, currently and in the foreseeable future, is their intermediate size ( approximately 500-5000 data points). This creates a number of issues in relation to error estimation. Initially we estimate the overall error in our trees based on standard cross-validation. However, this leaves out a significant fraction of the data in model construction and does not give error estimates on individual rules. Therefore, we present alternative methods to estimate the error in particular rules.

Animals↗

Analysis of yeast protein kinases using protein chips.

We have developed a novel protein chip technology that allows the high-throughput analysis of biochemical activities, and used this approach to analyse nearly all of the protein kinases from Saccharomyces cerevisiae. Protein chips are disposable arrays of microwells in silicone elastomer sheets placed on top of microscope slides. The high density and small size of the wells allows for high-throughput batch processing and simultaneous analysis of many individual samples. Only small amounts of protein are required. Of 122 known and predicted yeast protein kinases, 119 were overexpressed and analysed using 17 different substrates and protein chips. We found many novel activities and that a large number of protein kinases are capable of phosphorylating tyrosine. The tyrosine phosphorylating enzymes often share common amino acid residues that lie near the catalytic region. Thus, our study identified a number of novel features of protein kinases and demonstrates that protein chip technology is useful for high-throughput screening of protein biochemical activity.

Adenosine Triphosphate↗

Physiologic evaluation of pressure support ventilation by nasal mask in patients with stable COPD.

We evaluated the physiologic effects of pressure support ventilation by nasal route (NPSV) in eight patients with severe stable COPD and chronic hypercapnia who were randomly submitted to 2-h sessions of NPSV both with a portable ventilator (Respironics BIPAP device) and with a standard ventilator (Bird 6400ST device) at an inspiratory airway pressure of 22 cm H2O. Two sessions with each ventilator were performed using an FIO2 of 0.21 in each patient on two consecutive days. One patient did not tolerate either form of ventilation. Comparison of spontaneous with BIPAP ventilation showed a significant improvement in pH, PaCO2, and PaO2. Ventilatory pattern assessed by a respiratory inductive plethysmograph showed a significant increase in minute ventilation (VE), VT, and Ttot. Integrated surface diaphragmatic EMG activity measured only during BIPAP device ventilation decreased from that measured during spontaneous breathing. Similar changes in blood gases and ventilatory pattern were observed during ventilation by the Bird 6400ST except for VT/Ti ratio, which significantly increased. Comparison of baseline with measurements performed 12 h after the whole cycle of treatment showed a significant increase in pH and VE and a decrease in PaCO2. We conclude that short-term NPSV may be useful in improving respiratory pattern and blood gases in stable COPD patients with chronic hypercapnia.

Humans↗

[Value and limitations of radiography in dental implantology].

Numerous studies have been done on the subject of the biological, histological and clinical reactions concerned with the insertion of dental implants. The method and techniques used by various authors, based on various parameters, are hardly comparable. Also the estimated criterious of the results obtained are often influenced by a tendency to a personal interpretation varying considerably from one author to another. It is thus difficult to compare the results of studies, where the observation protocols have nothing in common with them, especially where X-ray examination is concerned. The papers which place the emphasis on the X-ray exams of the dental implantology, being few and unalike, it seemed interesting to put into evidence the X-ray indications, to state exactly the techniques and particularly to show the limits that concern the diagnosis, the pre- and postoperative control and the assessment of the clinical success. This work tries to lay down some guide lines may be of use to the practitioner.

Dental Implantation↗