Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

AIM To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224

The formation of a European identity through a transnational public sphere? The case of three Western European cultural journals, 1989-2006

This thesis analyses processes of discursive European identity formation in three cultural journals: Esprit, from France, the British New Left Review and the German Merkur during the time periods 1989-92, and, a decade later, during 2003-06. The theoretical framework which the thesis brings to bear on this analysis is that of the European Public Sphere. This model builds on Jürgen Habermas’s original model of a “public sphere”, and alleges that a sphere of common debate about issues of European concern can lead to a more defined and integrated sense of a European identity which is widely perceived as vague and inchoate. The relevancy of the public sphere model and its connection to the larger debate about European identity, especially since 1989, are discussed in the first part of the thesis. The second part provides a comparative analysis of the main European debates in the journals during the respective time periods. It outlines the mechanisms by which identity is expressed and assesses when, and to what extent, shared notions of European identity emerge. The analysis finds that identity formation does not occur through a developmental, gradual convergence of views as the European public sphere model envisages. Rather, it is brought about in much more haphazard back-and-forth movements. Moreover, shared notions of European identity between all the journals only arise in moments of perceived crises. Such crises are identified as the most salient factor which galvanizes expressions of a common, shared sense of European identity across national boundaries and ideological cleavages. The thesis concludes that the model of the EPS is too dependent on a partial view of how identity formation occurs and should thus adopt a more nuanced understanding about the complex factors that are at play in these processes. For the principled attempt to circumscribe identity formation as the outcome of communicative processes alone is likely to be thwarted by external events

Kulturelle Differenz und Versöhnung. Die Herausforderung der Toleranz

Seibert L. Kulturelle Differenz und Versöhnung. Die Herausforderung der Toleranz. In: Hauswedell C, Evangelische Akademie Loccum, eds. Frieden und Gerechtigkeit –- Dilemmata heutiger Friedensethik und -politik. Zur Diskussion der Denkschrift der EKD. Loccumer Protokolle. Vol [20]08,24. Rehburg-Loccum: Evangelische Akademie; 2009: 230

DREAM-Yara: an exact read mapper for very large databases with short update time

Motivation Mapping-based approaches have become limited in their application to very large sets of references since computing an FM-index for very large databases (e.g. >10 GB) has become a bottleneck. This affects many analyses that need such index as an essential step for approximate matching of the NGS reads to reference databases. For instance, in typical metagenomics analysis, the size of the reference sequences has become prohibitive to compute a single full-text index on standard machines. Even on large memory machines, computing such index takes about 1 day of computing time. As a result, updates of indices are rarely performed. Hence, it is desirable to create an alternative way of indexing while preserving fast search times. Results To solve the index construction and update problem we propose the DREAM (Dynamic seaRchablE pArallel coMpressed index) framework and provide an implementation. The main contributions are the introduction of an approximate search distributor via a novel use of Bloom filters. We combine several Bloom filters to form an interleaved Bloom filter and use this new data structure to quickly exclude reads for parts of the databases where they cannot match. This allows us to keep the databases in several indices which can be easily rebuilt if parts are updated while maintaining a fast search time. The second main contribution is an implementation of DREAM-Yara a distributed version of a fully sensitive read mapper under the DREAM framework. Availability and implementation: https://gitlab.com/pirovc/dream_yara