Motivation: Proteins with solenoid repeats evolve more quickly than non-repetitive ones and their periodicity may be rapidly hidden at sequence level, while still evident in structure. In order to identify these repeats, we propose here a novel method based on a metric characterizing amino-acid properties (polarity, secondary structure, molecular volume, codon diversity, electric charge) using five previously derived numerical functions.Results: The five spectra of the candidate sequences coding for structural repeats, obtained by Discrete Fourier Transform (DFT), show common features allowing determination of repeat periodicity with excellent results. Moreover it is possible to introduce a phase space parameterized by two quantities related to the Fourier spectra which allow for a clear distinction between a non-homologous set of globular proteins and proteins with solenoid repeats. The DFT method is shown to be competitive with other state of the art methods in the detection of solenoid structures, while improving its performance especially in the identification of periodicities, since it is able to recognize the actual repeat length in most cases. Moreover it highlights the relevance of local structural propensities in determining solenoid repeats.Availability: A web tool implementing the algorithm presented in the article (REPETITA) is available with additional details on the data sets at the URL: http://protein.bio.unipd.it/repetita/.Contact: silvio.tosatto@unipd.it

Here we introduce RAPHAEL, a novel method for the detection of solenoids in protein structures. It reliably solves three problems of increasing difficulty: (1) recognition of solenoid domains, (2) determination of their periodicity and (3) assignment of insertions. RAPHAEL uses a geometric approach mimicking manual classification, producing several numeric parameters that are optimized for maximum performance. The resulting method is very accurate, with 89.5% of solenoid proteins and 97.2% of non-solenoid proteins correctly classified. RAPHAEL periodicities have a Spearman correlation coefficient of 0.877 against the manually established ones. A baseline algorithm for insertion detection in identified solenoids has a Q(2) value of 79.8%, suggesting room for further improvement. RAPHAEL finds 1931 highly confident repeat structures not previously annotated as solenoids in the Protein Data Bank records.

The TESE server is available for non-commercial use at URL: http://protein.bio.unipd.it/tese/.

Myxoid liposarcoma (M-LS) is one of the most common soft tissue sarcomas in adults. Approximately 90% of cases show the characteristic t(12;16)(q13;p11) translocation, which produces the FUS-CHOP (FC) oncogene. FUS is a RNA-binding protein expressed in several tissues; CHOP a bZIP transcription factor involved in adipocyte differentiation. Although it is known that CHOP bZIP region is essential for FC-induced transformation, little is known about FC transcriptional targets and how FC participates in the development and progression of M-LS. Moreover, it is unclear whether FC controls the transcription of a set of genes different from the set controlled by CHOP. Understanding how the FUS-CHOP fusion protein causes M-LS will aid in the development of novel targeted therapies. To shed light on this issue we sought to exploit the ChIP-Seq technique (Chromatin Immunoprecipitation followed by next generation sequencing). To this end, chromatin immunorecipitation was performed on cell lines expressing FC (endogenous or ectopic). DNA co-precipitated together with the FC protein was analyzed by using an Illumina GAIIX platform. FC-bound DNA was mapped to the genome using the aligner Bowtie and the enriched regions were identified by using the MACS peak caller. ChIP-Seq data were combined with RNA-seq analysis to screen for the potential targets. Our approach was validated by the identification of LONP1, CLCN3 and GADD34, which have been previously reported to be modulated by CHOP. The most interesting candidates will be further investigated for their implication in FC development and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4197. doi:1538-7445.AM2012-4197