Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e−8 and 1.5e−9 per nucleotide per generation for SNVs and indels, respectively.

Predictions of intramolecular residue-residue contacts were assessed as part of the seventh community-wide Critical Assessment of Structure Prediction experiment (CASP7). As in past assessments, we focused on contacts that lie far apart in sequence as these are likely to be more informative in predicting protein structure. One lab did somewhat better than others according to our assessment, and there is some reason to think that this lab's results represent progress over CASP6. In general, contacts inferred from 3D structural predictions are similar in accuracy to those predicted by contact prediction methods. However, contact prediction methods were more accurate for some targets.

This article details the assessment process and evaluation results for two categories in the 8th Critical Assessment of Protein Structure Prediction experiment (CASP8). The domain prediction category was evaluated with a range of scores including the Normalized Domain Overlap score and a domain boundary distance measure. Residue‐residue contact predictions were evaluated with standard CASP measures, prediction accuracy, and Xd. In the domain boundary prediction category, prediction methods still make reliable predictions for targets that have structural templates, but continue to struggle to make good predictions for the few ab initio targets in CASP. There was little indication of improvement in the domain prediction category. The contact prediction category demonstrated that there was renewed interest among predictors and despite the small sample size the results suggested that there had been an increase in prediction accuracy. In contrast to CASP7 contact specialists predicted contacts more accurately than the majority of tertiary structure predictors. Despite this small success, the lack of free modeling targets makes it unlikely that either category will be included in their present form in CASP9. Proteins 2009. © 2009 Wiley‐Liss, Inc.

Purpose of review: Systemic lupus erythematosus (SLE) is caused by a combination of genetic and acquired immuno-deficiencies and environmental factors including infections. An association to Epstein-Barr virus (EBV) has been established by numerous studies over the past decades. Here, we review recent experimental studies on this, and present our integrated theory of SLE development. Recent findings: SLE patients have dysfunctional control of EBV infection resulting in frequent reactivationsand disease progression. These comprise impaired functions of EBV-specific T-cells with an inverse correlation to disease activity and elevated serum levels of antibodies against lytic cycle EBV antigens. The presence of EBV proteins in renal tissue from SLE patients with nephritis indicates a direct involvement of EBV in SLE development. As expected for patients with immuno-deficiencies, studies reveal that SLE patients show dysfunctional responses to other viruses as well. An association to EBV infection has also been demonstrated for other autoimmune diseases including Sjögren's syndrome, rheumatoid arthritis, and multiple sclerosis.Summary: Collectively, the interplay between an impaired immune system and the cumulative effects of EBV and other viruses results in frequent reactivations of EBV and enhanced cell death, causing development of SLE and concomitant autoreactivities.

Background: It has repeatedly been shown that interacting protein families tend to have similar phylogenetic trees. These similarities can be used to predicting the mapping between two families of interacting proteins (i.e. which proteins from one family interact with which members of the other). The correct mapping will be that which maximizes the similarity between the trees. The two families may eventually comprise orthologs and paralogs, if members of the two families are present in more than one organism. This fact can be exploited to restrict the possible mappings, simply by impeding links between proteins of different organisms. We present here an algorithm to predict the mapping between families of interacting proteins which is able to incorporate information regarding orthologues, or any other assignment of proteins to "classes" that may restrict possible mappings.