ELM—the database of eukaryotic linear motifs

Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instance

ELM--the database of eukaryotic linear motifs

Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.Author has checked copyrightDG 09/11/12Names (!) JG 2012-11-2

FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma

Integrated genomics approaches have revealed at least four distinct biologic variants of medulloblastoma: WNT (wingless), SHH (sonic hedgehog), group C, and group D. Because of the remarkable clinical heterogeneity of group D tumors and the dismal prognosis of group C patients, it is vital to identify molecular biomarkers that will allow early and effective treatment stratification in these non-WNT/non-SHH tumors. We combined transcriptome and DNA copy-number analyses for 64 primary medulloblastomas. Bioinformatic tools were used to discover marker genes of molecular variants. Differentially expressed transcripts were evaluated for prognostic value in the screening cohort. The prognostic power of follistatin-like 5 (FSTL5) immunopositivity was tested for 235 nonoverlapping medulloblastoma samples on two independent tissue microarrays. Comprehensive analyses of transcriptomic and genetic alterations delineate four distinct variants of medulloblastoma. Stable subgroup separation was achieved by using the 300 transcripts that varied the most. Distinct expression patterns of FSTL5 in each molecular subgroup were confirmed by quantitative real-time polymerase chain reaction. Immunopositivity of FSTL5 identified a large cohort of patients (84 of 235 patients; 36%) at high risk for relapse and death. Importantly, more than 50% of non-WNT/non-SHH tumors displayed FSTL5 negativity, delineating a large patient cohort with a good prognosis who would otherwise be considered intermediate or high-risk on the basis of current molecular subgrouping. FSTL5 expression denoted a dismal prognosis both within and across medulloblastoma subgroups. The addition of FSTL5 immunohistochemistry to existing molecular stratification schemes constitutes a reliable and cost-effective tool for prognostication in future clinical trials of medulloblastom

ELM--the database of eukaryotic linear motifs.

Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instance

Refined brain tumor diagnostics and stratified therapies: the requirement for a multidisciplinary approach

Individualized therapies are popular current concepts in oncology and first steps towards stratified medicine have now been taken in neurooncology through implementation of stratified therapeutic approaches. Knowledge about the molecular basis of brain tumors has expanded greatly in recent years and a few molecular alterations are studied routinely because of their clinical relevance. However, no single targeted agent has yet been fully approved for the treatment of glial brain tumors. In this review, we argue that multidisciplinary and integrated approaches are essential for translational research and the development of new treatments for patients with malignant gliomas, and we present a conceptual framework in which to place the components of such an interdisciplinary approach. We believe that this ambitious goal can be best realized through strong cooperation of brain tumor centers with local hospitals and physicians; such an approach enables close dialogue between expert subspecialty clinicians and local therapists to consider all aspects of this increasingly complex set of diseases