InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan search tool is now also available via a web service at http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html.

Rapid advances in DNA sequencing promise to enable new diagnostics and individualized therapies. Achieving personalized medicine, however, will require extensive research on highly reidentifiable, integrated datasets of genomic and health information. To assist with this, participants in the Personal Genome Project choose to forgo privacy via our institutional review board- approved “open consent” process. The contribution of public data and samples facilitates both scientific discovery and standardization of methods. We present our findings after enrollment of more than 1,800 participants, including whole-genome sequencing of 10 pilot participant genomes (the PGP-10). We introduce the Genome-Environment-Trait Evidence (GET-Evidence) system. This tool automatically processes genomes and prioritizes both published and novel variants for interpretation. In the process of reviewing the presumed healthy PGP-10 genomes, we find numerous literature references implying serious disease. Although it is sometimes impossible to rule out a late-onset effect, stringent evidence requirements can address the high rate of incidental findings. To that end we develop a peer production system for recording and organizing variant evaluations according to standard evidence guidelines, creating a public forum for reaching consensus on interpretation of clinically relevant variants. Genome analysis becomes a two-step process: using a prioritized list to record variant evaluations, then automatically sorting reviewed variants using these annotations. Genome data, health and trait information, participant samples, and variant interpretations are all shared in the public domain—we invite others to review our results using our participant samples and contribute to our interpretations. We offer our public resource and methods to further personalized medical research.

We present a new version of the European Bioinformatics Institute Web Services, a complete suite of SOAP-based web tools for structural and functional analysis, with new and improved applications. New functionality has been added to most of the services already available, and an improved version of the underlying framework has allowed us to include more applications. Information on the EBI Web Services, tutorials and clients can be found at http://www.ebi.ac.uk/Tools/webservices.

Drawing the epigenome landscape of Alzheimer’s disease (AD) still remains a challenge. To characterize the epigenetic molecular basis of the human hippocampus in AD, we profiled genome-wide DNA methylation levels in hippocampal samples from a cohort of pure AD patients and controls by using the Illumina 450K methylation arrays. Up to 118 AD-related differentially methylated positions (DMPs) were identified in the AD hippocampus, and extended mapping of specific regions was obtained by bisulfite cloning sequencing. AD-related DMPs were significantly correlated with phosphorylated tau burden. Functional analysis highlighted that AD-related DMPs were enriched in poised promoters that were not generally maintained in committed neural progenitor cells, as shown by ChiP-qPCR experiments. Interestingly, AD-related DMPs preferentially involved neurodevelopmental and neurogenesis-related genes. Finally, InterPro ontology analysis revealed enrichment in homeobox-containing transcription factors in the set of AD-related DMPs. These results suggest that altered DNA methylation in the AD hippocampus occurs at specific regulatory regions crucial for neural differentiation supporting the notion that adult hippocampal neurogenesis may play a role in AD through epigenetic mechanisms.

We studied the effect of stimulus predictability on the alpha and beta changes observed in central regions during stimulus-induced movement paradigms. Six young volunteers were instructed to extend briskly their dominant wrist as soon as possible after hearing a 2000 Hz sound. Two sequences of stimuli were presented to each subject, the first rhythmic at 1/6 s and the second with random intervals between 5 and 13s. A time-frequency analysis of nonphase-locked activity in the 7-37 Hz range was performed on stimulus-centred EEG sweeps using wavelet filters and Gabor transforms. During the sequence of predictable rhythmic stimuli, stimulus-induced movements were accompanied by a decrease in beta activity that began contralaterally about 1 s prior to the stimulus and extended to both sides later on. This decrease was followed by a rebound after the end of the movement. In the alpha band, the decrease observed started just after the sound. During the sequence of non-predictable, random stimuli, stimulus-induced movements were accompanied by a shorter and smaller alpha and beta-ERD, that started after the stimulus. The presence of a pre-stimulus beta ERD only in the rhythmic predictable paradigm suggests that central pre-movement beta ERD may be an indicator of motor preparation, and could be used for objective evaluation of time estimation and motor timing. The minimal differences observed in the alpha changes in both paradigms suggest that alpha-ERD may not be linked to motor preparation.