Quantifying the Displacement of Mismatches in Multiple Sequence Alignment Benchmarks

Multiple Sequence Alignment (MSA) methods are typically benchmarked on sets of reference alignments. The quality of the alignment can then be represented by the sum-of-pairs (SP) or column (CS) scores, which measure the agreement between a reference and corresponding query alignment. Both the SP and CS scores treat mismatches between a query and reference alignment as equally bad, and do not take the separation into account between two amino acids in the query alignment, that should have been matched according to the reference alignment. This is significant since the magnitude of alignment shifts is often of relevance in biological analyses, including homology modeling and MSA refinement/manual alignment editing. In this study we develop a new alignment benchmark scoring scheme, SPdist, that takes the degree of discordance of mismatches into account by measuring the sequence distance between mismatched residue pairs in the query alignment. Using this new score along with the standard SP score, we investigate the discriminatory behavior of the new score by assessing how well six different MSA methods perform with respect to BAliBASE reference alignments. The SP score and the SPdist score yield very similar outcomes when the reference and query alignments are close. However, for more divergent reference alignments the SPdist score is able to distinguish between methods that keep alignments approximately close to the reference and those exhibiting larger shifts. We observed that by using SPdist together with SP scoring we were able to better delineate the alignment quality difference between alternative MSA methods. With a case study we exemplify why it is important, from a biological perspective, to consider the separation of mismatches. The SPdist scoring scheme has been implemented in the VerAlign web server (http://www.ibi.vu.nl/programs/veralignwww/). The code for calculating SPdist score is also available upon request.     

Venous Drainage of the Femoral Neck in Legg Perthes Disease and in Hip Dysplasia

Three clinical cases of canine avascular femoral head necrosis and 4 cases of hip dysplasia were examined using intraosseus femoral neck venography. The contrast medium passed initio the diaphyseal bone marrow in all cases. Three growing dogs and 7 growing pigs were examined with the same method, before and after experimental ligation of the femoral veins. Before the venous tamponade, no contrast medium was visible in the femoral neck. The venography performed immediately after ligation showed contrast flow into the femoral neck similar to that seen in the clinical cases of Legg Perthes disease or hip dysplasia. However, a collateral circulation developed within 7 weeks. No more contrast-flow into the diaphysis was observed after that time. Although osteomedullography shows that both in Perthes disease and in hip dysplasia venous drainage has failed, venous tamponade may not induce the onset of the disease.