Local alignment of two-base encoded DNA sequence

<p>Abstract</p> <p>Background</p> <p>DNA sequence comparison is based on optimal local alignment of two sequences using a similarity score. However, some new DNA sequencing technologies do not directly measure the base sequence, but rather an encoded form, such as the two-base encoding considered here. In order to compare such data to a reference sequence, the data must be decoded into sequence. The decoding is deterministic, but the possibility of measurement errors requires searching among all possible error modes and resulting alignments to achieve an optimal balance of fewer errors versus greater sequence similarity.</p> <p>Results</p> <p>We present an extension of the standard dynamic programming method for local alignment, which simultaneously decodes the data and performs the alignment, maximizing a similarity score based on a weighted combination of errors and edits, and allowing an affine gap penalty. We also present simulations that demonstrate the performance characteristics of our two base encoded alignment method and contrast those with standard DNA sequence alignment under the same conditions.</p> <p>Conclusion</p> <p>The new local alignment algorithm for two-base encoded data has substantial power to properly detect and correct measurement errors while identifying underlying sequence variants, and facilitating genome re-sequencing efforts based on this form of sequence data.</p

Genetic Resistance to Rhabdovirus Infection in Teleost Fish Is Paralleled to the Derived Cell Resistance Status

Genetic factors of resistance and predisposition to viral diseases explain a significant part of the clinical variability observed within host populations. Predisposition to viral diseases has been associated to MHC haplotypes and T cell immunity, but a growing repertoire of innate/intrinsic factors are implicated in the genetic determinism of the host susceptibility to viruses. In a long-term study of the genetics of host resistance to fish rhabdoviruses, we produced a collection of double-haploid rainbow trout clones showing a wide range of susceptibility to Viral Hemorrhagic Septicemia Virus (VHSV) waterborne infection. The susceptibility of fibroblastic cell lines derived from these clonal fish was fully consistent with the susceptibility of the parental fish clones. The mechanisms determining the host resistance therefore did not associate with specific host immunity, but rather with innate or intrinsic factors. One cell line was resistant to rhabdovirus infection due to the combination of an early interferon IFN induction - that was not observed in the susceptible cells - and of yet unknown factors that hamper the first steps of the viral cycle. The implication of IFN was well consistent with the wide range of resistance of this genetic background to VSHV and IHNV, to the birnavirus IPNV and the orthomyxovirus ISAV. Another cell line was even more refractory to the VHSV infection through different antiviral mechanisms. This collection of clonal fish and isogenic cell lines provides an interesting model to analyze the relative contribution of antiviral pathways to the resistance to different viruses

Extracting sea level residual in tidally dominated estuarine environments

Sea level comprises a mean level, tidal elevation and a residual elevation. Knowledge of what causes maximum water levels is often key in coastal management. However, different methods to extract deviations in water level (residuals) from modelled and observed elevation can give different results. The Dee Estuary, northwest England is a macrotidal estuary that undergoes periodic stratification. It is used here to demonstrate methods to extract the residual water level in response to the following interactive processes: tidal, river-induced stratification and flow, meteorology and waves. Using modelling techniques, the interaction and contribution of different physical processes are investigated. Classical harmonic tidal analysis, model simulations and filtering techniques have been used to “de-tide” the total elevation for short-term (approximately month long) records. Each technique gives a different result highlighting the need to select the correct method for a required study. Analysis of the residual components demonstrates that all processes inducing residuals interact with the tide generating a semi-diurnal residual component. It is suggested that modelling methods enable the full effect of tidal interaction to remain in the residual, whilst harmonic tidal analysis (partly) modify and filtering methods (fully) remove this component of the residual. The analysis methods presented and their influences on the resultant residual are applicable to other study sites. However, when applied specifically to the mouth of the Dee Estuary, the external surge is found to be the main contributor to the total residual, whilst local wind and stratification effects are of secondary importance