Equipped with its 302-cell nervous system, the nematode Caenorhabditis elegans adapts its locomotion in different environments, exhibiting so-called swimming in liquids and crawling on dense gels. Recent experiments have demonstrated that the worm displays the full range of intermediate behaviors when placed in intermediate environments. The continuous nature of this transition strongly suggests that these behaviors all stem from modulation of a single underlying mechanism. We present a model of C. elegans forward locomotion that includes a neuromuscular control system that relies on a sensory feedback mechanism to generate undulations and is integrated with a physical model of the body and environment. We find that the model reproduces the entire swim-crawl transition, as well as locomotion in complex and heterogeneous environments. This is achieved with no modulatory mechanism, except via the proprioceptive response to the physical environment. Manipulations of the model are used to dissect the proposed pattern generation mechanism and its modulation. The model suggests a possible role for GABAergic D-class neurons in forward locomotion and makes a number of experimental predictions, in particular with respect to non-linearities in the model and to symmetry breaking between the neuromuscular systems on the ventral and dorsal sides of the body.

No abstract

Supplementary data are available at Bioinformatics online.

Background: The WRKY transcription factor gene family has a very ancient origin and has undergone extensive duplications in the plant kingdom. Several studies have pointed out their involvement in a range of biological processes, revealing that a large number of WRKY genes are transcriptionally regulated under conditions of biotic and/or abiotic stress. To investigate the existence of WRKY co-regulatory networks in plants, a whole gene family WRKYs expression study was carried out in rice (Oryza sativa). This analysis was extended to Arabidopsis thaliana taking advantage of an extensive repository of gene expression data.

Array comparative genomic hybridisation (aCGH) profiling is currently the gold standard for genetic diagnosis of copy number. Next generation sequencing technologies provide an alternative and adaptable method of detecting copy number by comparing the number of sequence reads in non-overlapping windows between patient and control samples. Detection of copy number using the BlueGnome 8×60k oligonucleotide aCGH platform was compared with low resolution next generation sequencing using the Illumina GAIIx on 39 patients with developmental delay and/or learning difficulties who were referred to the Leeds Clinical Cytogenetics Laboratory. Sensitivity and workflow of the two platforms were compared. Customised copy number algorithms assessed sequence counts and detected changes in copy number. Imbalances detected on both platforms were compared. Of the thirty-nine patients analysed, all eleven imbalances detected by array CGH and confirmed by FISH or Q-PCR were also detected by CNV-seq. In addition, CNV-seq reported one purported pathogenic copy number variant that was not detected by array CGH. Non-pathogenic, unconfirmed copy number calls were detected by both platforms; however few were concordant between the two. CNV-seq offers an alternative to array CGH for copy number analysis with resolution and future costs comparable to conventional array CGH platforms and with less stringent sample requirements.

A collection of 1373 unique flanking sequence tags (FSTs), generated from Ac/Ds and Ac transposon lines for reverse genetics studies, were produced in japonica and indica rice, respectively. The Ds and Ac FSTs together with the original T-DNAs were assigned a position in the rice genome sequence represented as assembled pseudomolecules, and found to be distributed evenly over the entire rice genome with a distinct bias for predicted gene-rich regions. The bias of the Ds and Ac transposon inserts for genes was exemplified by the presence of 59% of the inserts in genes annotated on the rice chromosomes and 41% present in genes transcribed as disclosed by their homology to cDNA clones. In a screen for inserts in a set of 75 well annotated transcription factors, including homeobox-containing genes, we found six Ac/Ds inserts. This high frequency of Ds and Ac inserts in genes suggests that saturated knockout mutagenesis in rice using this strategy will be efficient and possible with a lower number of inserts than expected. These FSTs and the corresponding plant lines are publicly available through OrygenesDB database and from the EU consortium members.

Human papillomavirus (HPV) infection in cases of squamous cell carcinoma of the oropharynx is a powerful predictive and prognostic biomarker. We describe how the use of next-generation sequencing can provide a novel method for the detection of HPV in DNA isolated from formalin-fixed paraffin-embedded tissues. Using this methodology in a cohort of 44 head and neck tumors, we identified the samples that contained HPV sequences, the viral subtype involved, and a direct readout of viral load. Specificity of HPV detection by sequencing compared to traditional detection methods using either PCR or p16 immunohistochemistry was 100%. Sensitivity was 50% when either compared to PCR [confidence interval (CI) = 29% to 71%] or 75% when compared to p16 (CI = 47% to 91%). In addition, we demonstrate the ability of next-generation sequencing to detect other HPV subtypes that would not have been detected by traditional methods, and we demonstrated the ability to apply this method to any tumor and any virus in a panel of eight human cancer cell lines. This methodology also provides a tumor genomic copy number karyogram, and in the samples analyzed here, a lower level of chromosome instability was detected in HPV-positive tumors compared to HPV-negative tumors, as observed in previous studies. Thus, the use of next-generation sequencing for the detection of HPV provides a multiplicity of data with clinical significance in a single test.

The study of the relationships between pre-cancer and cancer and identification of early driver mutations is becoming increasingly important as the value of molecular markers of early disease and personalised drug targets is recognised, especially now the extent of clonal heterogeneity in fully invasive disease is being realised. It has been assumed that pre-cancerous lesions exhibit a fairly passive progression to invasive disease; the degree to which they too are heterogeneous is unknown.We performed ultra-deep sequencing of thousands of selected mutations together with copy number analysis from multiple, matched pre-invasive lesions, primary tumours and metastases from five patients with oral cancer, some with multiple primary tumours presenting either synchronously or metachronously, totalling 75 samples. This allowed the clonal relationships between the samples to be observed for each patient.We expose for the first time the unexpected variety and complexity of the relationships between this group of oral dysplasias and their associated carcinomas, and ultimately, the diversity of processes by which tumours are initiated, spread and metastasise.Instead of a series of genomic precursors of their adjacent invasive disease, we have shown dysplasia to be a distinct dynamic entity, refuting the belief that pre-cancer and invasive tumours with a close spatial relationship always have linearly-related genomes. We show that oral pre-cancer exhibits considerable sub-clonal heterogeneity in its own right, that mutational changes in pre-cancer do not predict the onset of invasion, and that the genomic pathway to invasion is neither unified nor predictable.