Biomedical subjects

Julien Lagarde

Publications and source records attributed to Julien Lagarde.

5 recordsLinked to original sources

PubMed2006

EGASP: the human ENCODE Genome Annotation Assessment Project.

BACKGROUND: We present the results of EGASP, a community experiment to assess the state-of-the-art in genome annotation within the ENCODE regions, which span 1% of the human genome sequence. The experiment had two major goals: the assessment of the accuracy of computational methods to predict protein coding genes; and the overall assessment of the completeness of the current human genome annotations as represented in the ENCODE regions. For the computational prediction assessment, eighteen groups contributed gene predictions. We evaluated these submissions against each other based on a 'reference set' of annotations generated as part of the GENCODE project. These annotations were not available to the prediction groups prior to the submission deadline, so that their predictions were blind and an external advisory committee could perform a fair assessment. RESULTS: The best methods had at least one gene transcript correctly predicted for close to 70% of the annotated genes. Nevertheless, the multiple transcript accuracy, taking into account alternative splicing, reached only approximately 40% to 50% accuracy. At the coding nucleotide level, the best programs reached an accuracy of 90% in both sensitivity and specificity. Programs relying on mRNA and protein sequences were the most accurate in reproducing the manually curated annotations. Experimental validation shows that only a very small percentage (3.2%) of the selected 221 computationally predicted exons outside of the existing annotation could be verified. CONCLUSION: This is the first such experiment in human DNA, and we have followed the standards established in a similar experiment, GASP1, in Drosophila melanogaster. We believe the results presented here contribute to the value of ongoing large-scale annotation projects and should guide further experimental methods when being scaled up to the entire human genome sequence.

Alternative Splicing↗

PubMed2006

GENCODE: producing a reference annotation for ENCODE.

BACKGROUND: The GENCODE consortium was formed to identify and map all protein-coding genes within the ENCODE regions. This was achieved by a combination of initial manual annotation by the HAVANA team, experimental validation by the GENCODE consortium and a refinement of the annotation based on these experimental results. RESULTS: The GENCODE gene features are divided into eight different categories of which only the first two (known and novel coding sequence) are confidently predicted to be protein-coding genes. 5' rapid amplification of cDNA ends (RACE) and RT-PCR were used to experimentally verify the initial annotation. Of the 420 coding loci tested, 229 RACE products have been sequenced. They supported 5' extensions of 30 loci and new splice variants in 50 loci. In addition, 46 loci without evidence for a coding sequence were validated, consisting of 31 novel and 15 putative transcripts. We assessed the comprehensiveness of the GENCODE annotation by attempting to validate all the predicted exon boundaries outside the GENCODE annotation. Out of 1,215 tested in a subset of the ENCODE regions, 14 novel exon pairs were validated, only two of them in intergenic regions. CONCLUSION: In total, 487 loci, of which 434 are coding, have been annotated as part of the GENCODE reference set available from the UCSC browser. Comparison of GENCODE annotation with RefSeq and ENSEMBL show only 40% of GENCODE exons are contained within the two sets, which is a reflection of the high number of alternative splice forms with unique exons annotated. Over 50% of coding loci have been experimentally verified by 5' RACE for EGASP and the GENCODE collaboration is continuing to refine its annotation of 1% human genome with the aid of experimental validation.

Chromosome Mapping↗

PubMed2006

[Coordination dynamics: (in)stability and metastability in the behavioural and neural systems].

For more than 20 years, coordination dynamics have provided research on human movement science with new views about the nonlinear relationships between behavioral and neural dynamics. A number of studies across various experimental settings including bimanual, postural or interpersonal coordination, and also coordination between movements of a limb and an external event in the environment revealed the self-organized nature of human coordination. Here we review an extensive body of literature - in the human movement science and the neuroscience fields - that has investigated the coordination dynamics of brain and behavior when individuals are involved in two rhythmic coordination patterns: synchronization (on-the-beat movements) and syncopation (in-between beats movements). When the frequency of movement approaches 2 Hz, the syncopation mode is destabilized and synchronization is spontaneously adopted. The abrupt change between the two patterns illustrates a phenomenon known as non-equilibrium phase transition. Phase transitions offer a novel entry point into the investigation of pattern formation (and dissolution) at both the behavioral and the cerebral levels as they illustrate the loss of stability of the system. Brain imaging methods (MEG, EEG and fMRI) were used to reveal the neural signatures of (in)stability underlying the differences between behavioral coordination patterns, and pointed at the role of self-organization and metastability principles in brain functioning. Relationships between behavioral and brain dynamics can therefore be investigated within a unified empirical and theoretical framework.

Animals↗

PubMed2004

ArrayProspector: a web resource of functional associations inferred from microarray expression data.

DNA microarray experiments have provided vast amounts of data which can be used for inferring gene function. However, most methods for predicting functional associations between genes from expression data are not suited to simultaneous analysis of multiple datasets, and a comprehensive resource of coexpression-based predictions is currently lacking. Here, we present an interactive web resource of gene associations predicted by applying a novel algorithm to all expression data in the Stanford Microarray Database. The underlying pre-computed database currently contains more than 200 000 high-confidence gene associations in 12 different species sampled from a broad taxonomic range. The resource allows every association to be inspected visually and can be accessed at http://www.bork.embl.de/ArrayProspector.

Algorithms↗

PubMed2002

Interactions between human explicit and implicit perceptual motor learning shown by kinematic variables.

The goal of this study was to investigate in non-impaired humans the interaction between explicit and implicit learning in a catching task. The situation presented probabilistic contingencies between visual signals and various final pathways of the target. Subjects were asked to practice the interception task for 320 trials. Explicit instructions describing the probabilistic rules were given prior to (11 subjects), or in the middle of (11 subjects), physical practice. Eleven subjects not provided with verbal instructions served as control subjects. We measured the combination between explicit verbal instructions and implicit learning via kinematics of the end-effector and an outcome measure (i.e. spatial error). The time when explicit instructions were given resulted in systematic changes in the spatio-temporal ordering of the action. These data suggested that analyzing the way the task is executed with scrutiny allows a new understanding of how the aforementioned learning systems interact.

Adult↗