CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.

Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P=0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P=0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD.

Automated recognition of intracellular organelles in confocal microscope images.

Recognition of the localisation of intracellular proteins is essential to the understanding of their function. It is usually made through knowledge of and comparison to the distribution of well-characterised intracellular organelles by experts in cell biology. We have automated this process in order to achieve a more objective and quantitative assessment of the protein distribution within the cell, which can be employed by the less experienced cell biologist and may be utilised as a training program for inexperienced users, or as a high throughput localisation program for novel genes in functional analysis. Here we describe the development and testing of a classification system based on a modular neural network trained with sets of confocal sections through cell lines fluorescently stained for markers of key intracellular structures. The system functioned well in spite of the variability in pattern that occurs between individual cells and performed with 97% accuracy, which gives us confidence in the method and in its future development. It is envisaged that this program will aid the design of further experiments utilising colocalisation with known organelle marker proteins, in order to confirm putative trafficking pathways and protein--protein interactions of the protein of interest.

The life sciences Global Image Database (GID).

Although a vast amount of life sciences data is generated in the form of images, most scientists still store images on extremely diverse and often incompatible storage media, without any type of metadata structure, and thus with no standard facility with which to conduct searches or analyses. Here we present a solution to unlock the value of scientific images. The Global Image Database (GID) is a web-based (http://www.gwer.ch/qv/gid/gid.ht m ) structured central repository for scientific annotated images. The GID was designed to manage images from a wide spectrum of imaging domains ranging from microscopy to automated screening. The annotations in the GID define the source experiment of the images by describing who the authors of the experiment are, when the images were created, the biological origin of the experimental sample and how the sample was processed for visualization. A collection of experimental imaging protocols provides details of the sample preparation, and labeling, or visualization procedures. In addition, the entries in the GID reference these imaging protocols with the probe sequences or antibody names used in labeling experiments. The GID annotations are searchable by field or globally. The query results are first shown as image thumbnail previews, enabling quick browsing prior to original-sized annotated image retrieval. The development of the GID continues, aiming at facilitating the management and exchange of image data in the scientific community, and at creating new query tools for mining image data.

'Size leap' algorithm: an efficient extraction of the longest common motifs from a molecular sequence set. Application to the DNA sequence reconstruction.

We propose a new method, called 'size leap' algorithm, of search for motifs of maximum size and common to two fragments at least. It allows the creation of a reduced database of motifs from a set of sequences whose size obeys the series of Fibonacci numbers. The convenience lies in the efficiency of the motif extraction. It can be applied in the establishment of overlap regions for DNA sequence reconstruction and multiple alignment of biological sequences. The method of complete DNA sequence reconstruction by extraction of the longest motifs ('anchor motifs') is presented as an application of the size leap algorithm. The details of a reconstruction from three sequenced fragments are given as an example.

MASH: an interactive program for multiple alignment and consensus sequence construction for biological sequences.

This paper presents a method for the multiple alignment of a sequence set. The MASH algorithm uses a non-redundant database of common motifs and an 'alignment priority' criterion that depends on the length and the occurrence frequency of the patterns in the set of sequences. This user-defined criterion allows the determination of the series of the patterns to be aligned. This program is applied to a fragment of envelope gene env gp120 for 20 isolates of the immunodeficiency virus. The multiplicity of alignments obtained by modifying the criterion parameters reveals different aspects of similarity between the sequences.

A computer program for the design of optimal synthetic oligonucleotide probes for protein coding genes.

A computer program has been written in FORTRAN 77 to locate on a protein sequence a region with optimum length and limited degeneracy in order to design artificial oligonucleotide probes for use in molecular cloning. In addition the program checks for regions of homology between this probe and any other base sequence found in nucleotide sequence data banks. There are options in the program to eliminate rare codons or to make preferential choices of bases in order to minimize the degeneracy of probes.