Meeting the International Health Regulations (2005) surveillance core capacity requirements at the subnational level in Europe: the added value of syndromic surveillance

BACKGROUND: The revised World Health Organization's International Health Regulations (2005) request a timely and all-hazard approach towards surveillance, especially at the subnational level. We discuss three questions of syndromic surveillance application in the European context for assessing public health emergencies of international concern: (i) can syndromic surveillance support countries, especially the subnational level, to meet the International Health Regulations (2005) core surveillance capacity requirements, (ii) are European syndromic surveillance systems comparable to enable cross-border surveillance, and (iii) at which administrative level should syndromic surveillance best be applied? DISCUSSION: Despite the ongoing criticism on the usefulness of syndromic surveillance which is related to its clinically nonspecific output, we demonstrate that it was a suitable supplement for timely assessment of the impact of three different public health emergencies affecting Europe. Subnational syndromic surveillance analysis in some cases proved to be of advantage for detecting an event earlier compared to national level analysis. However, in many cases, syndromic surveillance did not detect local events with only a small number of cases. The European Commission envisions comparability of surveillance output to enable cross-border surveillance. Evaluated against European infectious disease case definitions, syndromic surveillance can contribute to identify cases that might fulfil the clinical case definition but the approach is too unspecific to comply to complete clinical definitions. Syndromic surveillance results still seem feasible for comparable cross-border surveillance as similarly defined syndromes are analysed. We suggest a new model of implementing syndromic surveillance at the subnational level. In this model, syndromic surveillance systems are fine-tuned to their local context and integrated into the existing subnational surveillance and reporting structure. By enhancing population coverage, events covering several jurisdictions can be identified at higher levels. However, the setup of decentralised and locally adjusted syndromic surveillance systems is more complex compared to the setup of one national or local system. SUMMARY: We conclude that syndromic surveillance if implemented with large population coverage at the subnational level can help detect and assess the local and regional effect of different types of public health emergencies in a timely manner as required by the International Health Regulations (2005)

progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement

Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms.We describe a new method to align two or more genomes that have undergone rearrangements due to recombination and substantial amounts of segmental gain and loss (flux). We demonstrate that the new method can accurately align regions conserved in some, but not all, of the genomes, an important case not handled by our previous work. The method uses a novel alignment objective score called a sum-of-pairs breakpoint score, which facilitates accurate detection of rearrangement breakpoints when genomes have unequal gene content. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The new genome alignment algorithm demonstrates high accuracy in situations where genomes have undergone biologically feasible amounts of genome rearrangement, segmental gain and loss. We apply the new algorithm to a set of 23 genomes from the genera Escherichia, Shigella, and Salmonella. Analysis of whole-genome multiple alignments allows us to extend the previously defined concepts of core- and pan-genomes to include not only annotated genes, but also non-coding regions with potential regulatory roles. The 23 enterobacteria have an estimated core-genome of 2.46Mbp conserved among all taxa and a pan-genome of 15.2Mbp. We document substantial population-level variability among these organisms driven by segmental gain and loss. Interestingly, much variability lies in intergenic regions, suggesting that the Enterobacteriacae may exhibit regulatory divergence.The multiple genome alignments generated by our software provide a platform for comparative genomic and population genomic studies. Free, open-source software implementing the described genome alignment approach is available from http://gel.ahabs.wisc.edu/mauve

Gene function prediction from synthetic lethality networks via ranking on demand.

MOTIVATION: Synthetic lethal interactions represent pairs of genes whose individual mutations are not lethal, while the double mutation of both genes does incur lethality. Several studies have shown a correlation between functional similarity of genes and their distances in networks based on synthetic lethal interactions. However, there is a lack of algorithms for predicting gene function from synthetic lethality interaction networks. RESULTS: In this article, we present a novel technique called kernelROD for gene function prediction from synthetic lethal interaction networks based on kernel machines. We apply our novel algorithm to Gene Ontology functional annotation prediction in yeast. Our experiments show that our method leads to improved gene function prediction compared with state-of-the-art competitors and that combining genetic and congruence networks leads to a further improvement in prediction accuracy