297 research outputs found
Pitch determination considering laryngealization effects in spoken dialogs
A frequent phenomenon in spoken dialogs of the information seeking type are short elliptic utterances whose mood (declarative or interrogative) can only be distinguished by intonation. The main acoustic evidence is conveyed by the fundamental frequency or Fo-contour. Many algorithms for Fo determination have been reported in the literature. A common problem are irregularities of speech known as "laryngealizations". This article describes an approach based on neural network techniques for the improved determination of fundamental frequency. First, an improved version of our neural network algorithm for reconstruction of the voice source signal (glottis signal) is presented. Second, the reconstructed voice source signal is used as input to another neural network distinguishing the three classes "voiceless", "voiced non-laryngealized", and "voiced laryngealized". Third, the results are used to improve an existing Fo algorithm. Results of this approach are presented and discussed in the context of the application in a spoken dialog system
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Systematic evaluation of spliced alignment programs for RNA-seq data
High-throughput RNA sequencing is an increasingly accessible method for studying gene structure and activity on a genome-wide scale. A critical step in RNA-seq data analysis is the alignment of partial transcript reads to a reference genome sequence. To assess the performance of current mapping software, we invited developers of RNA-seq aligners to process four large human and mouse RNA-seq data sets. In total, we compared 26 mapping protocols based on 11 programs and pipelines and found major performance differences between methods on numerous benchmarks, including alignment yield, basewise accuracy, mismatch and gap placement, exon junction discovery and suitability of alignments for transcript reconstruction. We observed concordant results on real and simulated RNA-seq data, confirming the relevance of the metrics employed. Future developments in RNA-seq alignment methods would benefit from improved placement of multimapped reads, balanced utilization of existing gene annotation and a reduced false discovery rate for splice junctions
Oqtans: a Galaxy-integrated workflow for quantitative transcriptome analysis from NGS Data : From Seventh International Society for Computational Biology (ISCB) Student Council Symposium 2011 Vienna, Austria. 15 July 2011
First published by BioMed Central:
Schultheiss, Sebastian J.; Jean, Géraldine; Behr, Jonas; Bohnert, Regina; Drewe, Philipp; Görnitz, Nico; Kahles, André; Mudrakarta, Pramod; Sreedharan, Vipin T.; Zeller, Georg; Rätsch, Gunnar: Oqtans: a Galaxy-integrated workflow for quantitative transcriptome analysis from NGS Data - In: BMC Bioinformatics. - ISSN 1471-2105 (online). - 12 (2011), suppl. 11, art. A7. - doi:10.1186/1471-2105-12-S11-A7
Alternative splicing substantially diversifies the transcriptome during early photomorphogenesis and correlates with the energy availability in arabidopsis
Plants use light as source of energy and information to detect diurnal rhythms and seasonal changes. Sensing changing light conditions is critical to adjust plant metabolism and to initiate developmental transitions. Here we analyzed transcriptome-wide alterations in gene expression and alternative splicing (AS) of etiolated seedlings undergoing photomorphogenesis upon exposure to blue, red, or white light. Our analysis revealed massive transcriptome reprograming as reflected by differential expression of ~20% of all genes and changes in several hundred AS events. For more than 60% of all regulated AS events, light promoted the production of a presumably protein-coding variant at the expense of an mRNA with nonsense-mediated decay-triggering features. Accordingly, AS of the putative splicing factor REDUCED RED-LIGHT RESPONSES IN CRY1CRY2 BACKGROUND 1 (RRC1), previously identified as a red light signaling component, was shifted to the functional variant under light. Downstream analyses of candidate AS events pointed at a role of photoreceptor signaling only in monochromatic but not in white light. Furthermore, we demonstrated similar AS changes upon light exposure and exogenous sugar supply, with a critical involvement of kinase signaling. We propose that AS is an integration point of signaling pathways that sense and transmit information regarding the energy availability in plants
Genomic Rearrangements in Arabidopsis Considered as Quantitative Traits.
To understand the population genetics of structural variants and their effects on phenotypes, we developed an approach to mapping structural variants that segregate in a population sequenced at low coverage. We avoid calling structural variants directly. Instead, the evidence for a potential structural variant at a locus is indicated by variation in the counts of short-reads that map anomalously to that locus. These structural variant traits are treated as quantitative traits and mapped genetically, analogously to a gene expression study. Association between a structural variant trait at one locus, and genotypes at a distant locus indicate the origin and target of a transposition. Using ultra-low-coverage (0.3×) population sequence data from 488 recombinant inbred Arabidopsis thaliana genomes, we identified 6502 segregating structural variants. Remarkably, 25% of these were transpositions. While many structural variants cannot be delineated precisely, we validated 83% of 44 predicted transposition breakpoints by polymerase chain reaction. We show that specific structural variants may be causative for quantitative trait loci for germination and resistance to infection by the fungus Albugo laibachii, isolate Nc14. Further we show that the phenotypic heritability attributable to read-mapping anomalies differs from, and, in the case of time to germination and bolting, exceeds that due to standard genetic variation. Genes within structural variants are also more likely to be silenced or dysregulated. This approach complements the prevalent strategy of structural variant discovery in fewer individuals sequenced at high coverage. It is generally applicable to large populations sequenced at low-coverage, and is particularly suited to mapping transpositions
DNA methylation variation in Arabidopsis has a genetic basis and shows evidence of local adaptation
Epigenome modulation in response to the environment potentially provides a
mechanism for organisms to adapt, both within and between generations. However,
neither the extent to which this occurs, nor the molecular mechanisms involved
are known. Here we investigate DNA methylation variation in Swedish Arabidopsis
thaliana accessions grown at two different temperatures. Environmental effects
on DNA methylation were limited to transposons, where CHH methylation was found
to increase with temperature. Genome-wide association mapping revealed that the
extensive CHH methylation variation was strongly associated with genetic
variants in both cis and trans, including a major trans-association close to
the DNA methyltransferase CMT2. Unlike CHH methylation, CpG gene body
methylation (GBM) on the coding region of genes was not affected by growth
temperature, but was instead strongly correlated with the latitude of origin.
Accessions from colder regions had higher levels of GBM for a significant
fraction of the genome, and this was correlated with elevated transcription
levels for the genes affected. Genome-wide association mapping revealed that
this effect was largely due to trans-acting loci, a significant fraction of
which showed evidence of local adaptation. These findings constitute the first
direct link between DNA methylation and adaptation to the environment, and
provide a basis for further dissecting how environmentally driven and
genetically determined epigenetic variation interact and influence organismal
fitness.Comment: 38 pages 4 figure
Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain
Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naive animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems
Genomic basis for RNA alterations in cancer
Transcript alterations often result from somatic changes in cancer genomes. Various forms of RNA alterations have been described in cancer, including overexpression, altered splicing and gene fusions; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer
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