BACKGROUND: Any method that de novo predicts protein function should do better than random. More challenging, it also ought to outperform simple homology-based inference. METHODS: Here, we describe a few methods that predict protein function exclusively through homology. Together, they set the bar or lower limit for future improvements. RESULTS AND CONCLUSIONS: During the development of these methods, we faced two surprises. Firstly, our most successful implementation for the baseline ranked very high at CAFA1. In fact, our best combination of homology-based methods fared only slightly worse than the top-of-the-line prediction method from the Jones group. Secondly, although the concept of homology-based inference is simple, this work revealed that the precise details of the implementation are crucial: not only did the methods span from top to bottom performers at CAFA, but also the reasons for these differences were unexpected. In this work, we also propose a new rigorous measure to compare predicted and experimental annotations. It puts more emphasis on the details of protein function than the other measures employed by CAFA and may best reflect the expectations of users. Clearly, the definition of proper goals remains one major objective for CAFA.

UNLABELLED: Many existing databases annotate experimentally characterized single nucleotide polymorphisms (SNPs). Each non-synonymous SNP (nsSNP) changes one amino acid in the gene product (single amino acid substitution;SAAS). This change can either affect protein function or be neutral in that respect. Most polymorphisms lack experimental annotation of their functional impact. Here, we introduce SNPdbe-SNP database of effects, with predictions of computationally annotated functional impacts of SNPs. Database entries represent nsSNPs in dbSNP and 1000 Genomes collection, as well as variants from UniProt and PMD. SAASs come from >2600 organisms; 'human' being the most prevalent. The impact of each SAAS on protein function is predicted using the SNAP and SIFT algorithms and augmented with experimentally derived function/structure information and disease associations from PMD, OMIM and UniProt. SNPdbe is consistently updated and easily augmented with new sources of information. The database is available as an MySQL dump and via a web front end that allows searches with any combination of organism names, sequences and mutation IDs. AVAILABILITY: http://www.rostlab.org/services/snpdbe.

MOTIVATION: The mutation of amino acids often impacts protein function and structure. Mutations without negative effect sustain evolutionary pressure. We study a particular aspect of structural robustness with respect to mutations: regular protein secondary structure and natively unstructured (intrinsically disordered) regions. Is the formation of regular secondary structure an intrinsic feature of amino acid sequences, or is it a feature that is lost upon mutation and is maintained by evolution against the odds? Similarly, is disorder an intrinsic sequence feature or is it difficult to maintain? To tackle these questions, we in silico mutated native protein sequences into random sequence-like ensembles and monitored the change in predicted secondary structure and disorder. RESULTS: We established that by our coarse-grained measures for change, predictions and observations were similar, suggesting that our results were not biased by prediction mistakes. Changes in secondary structure and disorder predictions were linearly proportional to the change in sequence. Surprisingly, neither the content nor the length distribution for the predicted secondary structure changed substantially. Regions with long disorder behaved differently in that significantly fewer such regions were predicted after a few mutation steps. Our findings suggest that the formation of regular secondary structure is an intrinsic feature of random amino acid sequences, while the formation of long-disordered regions is not an intrinsic feature of proteins with disordered regions. Put differently, helices and strands appear to be maintained easily by evolution, whereas maintaining disordered regions appears difficult. Neutral mutations with respect to disorder are therefore very unlikely.

Usage control is a generalization of access control that also addresses how data is handled after it is released. Usage control requirements are specified in policies. We present tool support for the following analysis problems. Is a policy consistent, i.e., satisfiable? Is an abstractly specified usage controlmechanism capable of enforcing a given policy? Can we configure such a mechanism by analyzing respective policies? In the context of propagation, where upon re-distribution of data duties may only be increased and rights decreased, can we check if a policy is only strengthened in this sense? — Our solution uses a modelchecker as theorem prover and is based on a translation ofusage control policies into a Linear Time Logic (LTL) dialect. We provide evidence that even complex policies can be analyzed efficiently.

Usage control is a generalization of access control that also addresses how data is used after it is released. We present a formal model for different mechanisms that can enforce usage control policies on the consumer side.

With the convergence of the Internet and the mobile communications world, Internet-based services may become available on any user device. In order to make efficient use of such a ubiquitous environment the user demands to access his personalized services from any place, anytime and on any device regardless of the type of access network. In particular, we consider the situation that a user transfers a running session between devices. We refer to this as session mobility. Providing such ubiquitous services transparently to the user, is not only challenging from a networking point of view but also poses severe requirements on the management operations and in particular accounting needed for a commercial service rollout. We describe an accounting architecture for session mobility. It allows the network operators to determine, collect and evaluate data on service usage when users transfer their ongoing communication session(s) from one device to another or a set of devices within its domain or across multiple operators' environments. In particular, we describe the interactions required between the signaling protocol and the accounting protocol in support of session mobility.

Accounting is an essential task for commercial service usage, determining the collection of metered data and correlating it into accounting records. The accounting data generated, describing the service usage of users, serves as input for the subsequent charging process. Because of the diversity of IP-based services and the variety of network technologies, a generic accounting management is required, specifically tailored to user and provider needs. A mobile and multi-domain environment determines additional challenges. This work defines a generic, technology-, and service-independent configuration management of accounting in a mobile, heterogeneous, and multi-provider environment. The proposed accounting process enables a user-and service-specific accounting configuration. It is based on the diameter protocol, specifying required extensions, which include new commands and attribute-value-pairs

The new accounting configuration management based on diameter is highly suitable for wireless and mobile communication systems. The diameter protocol extensions by new commands and new AVP's result in a complete and standard-conforming approach. This paper draws the conclusion that the service-oriented accounting configuration management proposed complies with all requirements defined. The common layer above any network access technology is the IP layer and all diameter extensions proposed fit well. User and service profiles enable mobile and wireless network operators to have the best available flexibility to add new services, assign new services to users, and, by providing the respective accounting definitions, have a user- and service-specific accounting configuration in place