Biomedical subjects

C Médigue

Publications and source records attributed to C Médigue.

29 records · Page 2Linked to original sources

PubMed1995

Cooperative computer system for genome sequence analysis.

Analysis of the huge volumes of data generated by large scale sequencing projects clearly requires the construction of new sophisticated computer systems. These systems should be able to handle the biological data as well as the results of the analysis of this data. They should also help the user to choose the most appropriate method for a simple task and to string together the methods needed to solve a global analysis task. In this paper we present the prototype of a software system that provides an environment for the analysis of large-scale sequence data. In a first approach this environment has been put to the test within the B. subtilis sequencing project. This system integrates both a descriptive knowledge of the entities involved (genes, regulatory signals etc.) and the methodological knowledge concerning an extendable set of analytical methods (i.e. how to solve a sequence analysis problem through task decomposition and method selection). A knowledge representation based on two existing object-oriented models, named Shirka and SCARP, is used to implement this integrated system. In addition, the present prototype provides a suitable user interface for both displaying the results generated by several methods and interacting with the objects. We present in this paper an overview of the knowledge-based models used to build this integrated system, and a description of the way in which biological entities and sequence analysis tasks are represented. We give illustrations of the co-operation between user and system during the problem solving process. Such a system constitutes a computer workbench for molecular biologists studying the genetic programs of living organisms.

Bacillus subtilis↗

PubMed1994

Heart rate and heart rate variability during sleep in small-for-gestational age newborns.

To assess the influence of intrauterine growth retardation on heart rate (HR) and HR variability during sleep, we performed polygraphic recordings in 10 small-for-gestational age (SGA) and 16 appropriate-for-gestational age (AGA) newborns. Both groups were clinically and neurologically normal and were at 37 to 41 wk conceptional age. RR intervals were analyzed using the short-time Fourier transform in three frequency bands: 1) high frequency, with a period 3-8 heartbeat; 2) mid frequency, with a period 10-25 heartbeat; and 3) low frequency, with a period 30-100 heartbeat. In both active and quiet sleep, SGA newborns significantly differed from AGA newborns by having a shorter RR interval (p < 0.01) and lower amplitude of HR variability in all bands (p < 0.05) except low frequency in quiet sleep. Quiet sleep differed from active sleep by having a longer RR interval (p < 0.05), higher high-frequency variability (p < 0.02) in both SGA and AGA newborns, and lower low-frequency variability (p < 0.005 for AGA newborns). Our data give evidence of clear modifications of both sympathetic and parasympathetic HR control in the at-risk SGA population. Similarity of between-state characteristics suggests maintained CNS control of HR in SGA as well as in AGA newborns. We speculate that between-group HR and HR variability differences may be related to augmented metabolic rate in SGA compared with AGA newborns.

Basal Metabolism↗

PubMed1993

Heart-rate variability in low-risk prematurely born infants reaching normal term: a comparison with full-term newborns.

To investigate the influence of prematurity and postnatal age on the maturation of the autonomic nervous system function, we analysed heart-rate and heart-rate variability in twelve prematurely born infants (< 37 weeks gestational age) reaching the conceptional age of 37-41 weeks. These neonates were compared with sixteen 37-41 week conceptional age newborns (< 10 days postnatal age). Heart-rate variability was analysed by spectral analysis of interbeat intervals using Short-Time Fourier Transform. We found that during both active and quiet sleep, the durations of RR-intervals were shorter and the amplitude of heart-rate variability in different frequency bands was lower in prematures reaching term than in newborns of the same conceptional age (P < 0.001). Between-state comparison showed differences in both groups. In both groups, low-frequency heart-rate variability was higher in active sleep than in quiet sleep. Between-state differences of RR-intervals and high-frequency heart-rate variability were present only in newborns (P < 0.01). Discrimination between newborns and prematures reaching term, based on RR-intervals and heart-rate variability, was correct in both sleep states with errors between 7 to 16%. However, in both newborns and prematures reaching term, between-state discrimination showed less reliable results, especially for quiet sleep discrimination with 24% (in PRT) and 20% (in NB) of errors. Our results, especially information given by factor analysis, suggest that the differences between newborns and prematures reaching term, concerning RR-interval and heart-rate variability, may be related to a changed balance between the sympathetic and parasympathetic nervous systems with a diminished parasympathetic component of heart rate control in prematures reaching term, as compared to newborns.

Discriminant Analysis↗

PubMed1993

Colibri: a functional data base for the Escherichia coli genome.

Several data libraries have been created to organize all the data obtained worldwide about the Escherichia coli genome. Because the known data now amount to more than 40% of the whole genome sequence, it has become necessary to organize the data in such a way that appropriate procedures can associate knowledge produced by experiments about each gene to its position on the chromosome and its relation to other relevant genes, for example. In addition, global properties of genes, affected by the introduction of new entries, should be present as appropriate description fields. A data base, implemented on Macintosh by using the data base management system 4th Dimension, is described. It is constructed around a core constituted by known contigs of E. coli sequences and links data collected in general libraries (unmodified) to data associated with evolving knowledge (with modifiable fields). Biologically significant results obtained through the coupling of appropriate procedures (learning or statistical data analysis) are presented. The data base is available through a 4th Dimension runtime and through FTP on Internet. It has been regularly updated and will be systematically linked to other E. coli data bases (M. Kroger, R. Wahl, G. Schachtel, and P. Rice, Nucleic Acids Res. 20(Suppl.):2119-2144, 1992; K. E. Rudd, W. Miller, C. Werner, J. Ostell, C. Tolstoshev, and S. G. Satterfield, Nucleic Acids Res. 19:637-647, 1991) in the near future.

Bacterial Proteins↗

PubMed1993

Building large knowledge bases in molecular biology.

Large scale genome sequencing projects are now producing hugh amounts of data which can be readily stored and managed within data base management systems, and analyzed using dedicated software packages. The results of these analyzes should also be stored with the input DNA sequences. The increasing complexity and size of the objects to be described and managed have led biologists to rely on advanced data models such as the object-oriented model. As a joint effort between our computer science and molecular biology research projects, the knowledge bases we have developed in molecular genetics have shown however that the basic object-oriented model is not fully adapted to the complexity of some biological situations encountered. Advanced descriptive capabilities, provided only by knowledge models originated from the AI field, are required. Composite or evolving objects, multiple viewpoints, constraints, tasks and methods, textual annotations are some examples of such capabilities. They are illustrated by biological situations for which they appeared to be necessary. Supporting powerful reasoning mechanisms (e.g. object classification, constraint propagation or qualitative simulators), they allow the development of large knowledge bases in molecular biology. These knowledge bases are expected to become the adequate support for co-operative distributed research efforts.

Artificial Intelligence↗

PubMed1992

Heart rate variability in normal sleeping full-term and preterm neonates.

To assess maturation of the Autonomic Nervous System (ANS) and sleep states, Heart Rate Variability (HRV) was studied in 24 healthy sleeping newborns, aged from 31 to 41 weeks, conceptional age (CA). Spectral analysis of the interbeat interval (RR) signal, was performed by Short-Time Fourier Transform, in three frequency bands: high (HF), of purely vagal origin, mid (MF), and low (LF), vagal and sympathetic, thus allowing evaluation of both branches of the ANS, observed in Active Sleep (AS = REM Sleep) and in Quiet Sleep (QS = nREM Sleep). Principal Component Analysis, Discriminant Analysis, and hypothesis tests were used to investigate the evolution of spectral variables and their relation with sleep states. HF, MF, LF, and mean RR all increased with age; the differences from the premature to the full-term group, were more marked, as a whole, in AS than in QS. HF showed the highest increase from the premature (31-36 weeks CA) to the intermediate (37-38) group, whereas LF showed equal differences from the premature to the intermediate, and from the intermediate to the full-term (39-41) groups. These results suggest a steep increase in vagal tone at 37-38 weeks CA, with stability afterwards, and a more regular increase in sympathetic tone from 31 to 41 weeks CA.

Analysis of Variance↗

PubMed1991

Evidence for horizontal gene transfer in Escherichia coli speciation.

After extracting more than 780 identified Escherichia coli genes from available data libraries, we investigated the codon usage of the corresponding coding sequences and extended the study of gene classes, thus obtained, to the nature and intensity of short nucleotide sequence selection, related to constraints operating at the nucleotide level. Using Factorial Correspondence Analysis we found that three classes ought to be included in order to match all data now available. The first two classes, as known, encompass genes expressed either continuously at a high level, or at a low level and/or rarely; the third class consists of genes corresponding to surface elements of the cell, genes coming from mobile elements as well as genes resulting in a high fidelity of DNA replication. This suggests that bacterial strains cultivated in the laboratory have been fixed by specific use of antimutator genes that are horizontally exchanged.

Amino Acids↗

PubMed1991

Escherichia coli molecular genetic map (1500 kbp): update II.

The DNA sequence data for Escherichia coli deposited in the EMBL library (release 27), together with miscellaneous data obtained from several laboratories, have been localized on an updated and corrected version of the restriction map of the chromosome generated by Kohara et al. (1987) and modified by others. This second update adds a further 500 kbp, increasing the amount of the E. coli chromosome sequenced to about one third of the total: 1510 kbp of sequenced DNA is included in the present data base. The accuracy of the map is assessed, and allows us to propose a precise genetic map position for every sequenced gene. The location of rare-cutting sites such as AvrII, NotI and SfiI have also been included in the update in order to combine the data obtained from different sources into one single file. The distribution of palindromic sequences (to which most restriction sites belong) has been studied in coding sequences. There appears to be a significant counter-selection against several such sequences in E. coli coding sequences (but not in other organisms such as Saccharomyces cerevisiae), suggesting the existence of constraints on DNA structure in E. coli, perhaps indicative of a functional role for horizontal gene transfer, preserving coding sequences, in this type of bacteria.

Base Sequence↗

PubMed1990

Mapping of sequenced genes (700 kbp) in the restriction map of the Escherichia coli chromosome.

This paper describes software (written in Pascal and running on Macintosh computers) allowing localization of unknown DNA fragments from the Escherichia coli chromosome on the restriction map established by Kohara et al. (1987). The program identifies the segment's map position using a restriction pattern analysis obtained with all, or some, of the eight enzymes used by Kohara et al. (1987). Therefore, the sequenced genes available in the EMBL library may be localized on the E. coli chromosome restriction map. This allowed correction of the map (mainly by introducing missing sites in the published maps) at the corresponding positions. Analysis of the data indicates that there is only a very low level of polymorphism, at the nucleotide level, between the E. coli K12 strains used by the various laboratories involved in DNA sequencing. The program is versatile enough to be used with other genomes.

Chromosome Inversion↗

PubMed1990

Escherichia coli molecular genetic map (1000 kbp): update I.

The sequenced genes from Escherichia coli that are available in the EMBL library (release 21) have been localized on an updated and corrected version of the restriction map of the chromosome generated by Kohara et al. (1987). One thousand kbp of sequenced DNA are incorporated in this update; this is equivalent to 23% of the total genome. The accuracy of the map is assessed, and it is corrected and updated where appropriate. A significant number of sites were missing from the original map, mainly involving two of the eight enzymes used by Kohara et al. (1987), ie. PvuII and EcoRV. The nucleotide environment of such missing sites was examined and, using an Artificial Intelligence approach, it appears that the site for these enzymes is sensitive to context effects. Several genes of known position on the E. coli chromosome could not be placed on the restriction map; this suggests that additional gaps are likely to exist on the restriction map, in addition to the original seven identified by Kohara et al. We have also obtained information about the probable direction of transcription of chromosomal genes with respect to the map. Most genes are transcribed in the same direction as the replication forks, particularly around oriC at 84 min.

Artificial Intelligence↗

PubMedDate not supplied

From data banks to data bases.

The information collected in national and international libraries on nucleotide and protein sequences cannot be directly treated for proper handling by existing software. Therefore we evaluated the feasibility of constructing a data base for Escherichia coli using the data present in the banks. The knowhow thus acquired was applied to Bacillus subtilis. Specific examples of the general procedure are given.

Bacillus subtilis↗