15 research outputs found
SERpredict: Detection of tissue- or tumor-specific isoforms generated through exonization of transposable elements
Background: Transposed elements (TEs) are known to affect transcriptomes,
because either new exons are generated from intronic transposed elements (this
is called exonization), or the element inserts into the exon, leading to a new
transcript. Several examples in the literature show that isoforms generated by
an exonization are specific to a certain tissue (for example the heart muscle)
or inflict a disease. Thus, exonizations can have negative effects for the
transcriptome of an organism. Results: As we aimed at detecting other tissue-
or tumor-specific isoforms in human and mouse genomes which were generated
through exonization of a transposed element, we designed the automated analysis
pipeline SERpredict (SER = Specific Exonized Retroelement) making use of
Bayesian Statistics. With this pipeline, we found several genes in which a
transposed element formed a tissue- or tumor-specific isoform. Conclusion: Our
results show that SERpredict produces relevant results, demonstrating the
importance of transposed elements in shaping both the human and the mouse
transcriptomes. The effect of transposed elements on the human transcriptome is
several times higher than the effect on the mouse transcriptome, due to the
contribution of the primate-specific Alu element
Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu's unique role in shaping the human transcriptome
Background: Transposed elements (TEs) have a substantial impact on mammalian
evolution and are involved in numerous genetic diseases. We compared the impact
of TEs on the human transcriptome and the mouse transcriptome. Results: We
compiled a dataset of all TEs in the human and mouse genomes, identifying
3,932,058 and 3,122,416 TEs, respectively. We than extracted TEs located within
human and mouse genes and, surprisingly, we found that 60% of TEs in both human
and mouse are located in intronic sequences, even though introns comprise only
24% of the human genome. All TE families in both human and mouse can exonize.
TE families that are shared between human and mouse exhibit the same percentage
of TE exonization in the two species, but the exonization level of Alu, a
primatespecific retroelement, is significantly greater than that of other TEs
within the human genome, leading to a higher level of TE exonization in human
than in mouse (1,824 exons compared with 506 exons, respectively). We detected
a primate-specific mechanism for intron gain, in which Alu insertion into an
exon creates a new intron located in the 3' untranslated region (termed
'intronization'). Finally, the insertion of TEs into the first and last exons
of a gene is more frequent in human than in mouse, leading to longer exons in
human. Conclusion: Our findings reveal many effects of TEs on these two
transcriptomes. These effects are substantially greater in human than in mouse,
which is due to the presence of Alu elements in human
Automatic detection of exonic splicing enhancers (ESEs) using SVMs
<p>Abstract</p> <p>Background</p> <p>Exonic splicing enhancers (ESEs) activate nearby splice sites and promote the inclusion (vs. exclusion) of exons in which they reside, while being a binding site for SR proteins. To study the impact of ESEs on alternative splicing it would be useful to have a possibility to detect them in exons. Identifying SR protein-binding sites in human DNA sequences by machine learning techniques is a formidable task, since the exon sequences are also constrained by their functional role in coding for proteins.</p> <p>Results</p> <p>The choice of training examples needed for machine learning approaches is difficult since there are only few exact locations of human ESEs described in the literature which could be considered as positive examples. Additionally, it is unclear which sequences are suitable as negative examples. Therefore, we developed a motif-oriented data-extraction method that extracts exon sequences around experimentally or theoretically determined ESE patterns. Positive examples are restricted by heuristics based on known properties of ESEs, e.g. location in the vicinity of a splice site, whereas negative examples are taken in the same way from the middle of long exons. We show that a suitably chosen SVM using optimized sequence kernels (e.g., combined oligo kernel) can extract meaningful properties from these training examples. Once the classifier is trained, every potential ESE sequence can be passed to the SVM for verification. Using SVMs with the combined oligo kernel yields a high accuracy of about 90 percent and well interpretable parameters.</p> <p>Conclusion</p> <p>The motif-oriented data-extraction method seems to produce consistent training and test data leading to good classification rates and thus allows verification of potential ESE motifs. The best results were obtained using an SVM with the combined oligo kernel, while oligo kernels with oligomers of a certain length could be used to extract relevant features.</p
Characteristics of transposable element exonization within human and mouse
Insertion of transposed elements within mammalian genes is thought to be an
important contributor to mammalian evolution and speciation. Insertion of
transposed elements into introns can lead to their activation as alternatively
spliced cassette exons, an event called exonization. Elucidation of the
evolutionary constraints that have shaped fixation of transposed elements
within human and mouse protein coding genes and subsequent exonization is
important for understanding of how the exonization process has affected
transcriptome and proteome complexities. Here we show that exonization of
transposed elements is biased towards the beginning of the coding sequence in
both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs)
revealed that exonization of transposed elements can be population-specific,
implying that exonizations may enhance divergence and lead to speciation. SNP
density analysis revealed differences between Alu and other transposed
elements. Finally, we identified cases of primate-specific Alu elements that
depend on RNA editing for their exonization. These results shed light on TE
fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure
Integration und Desintegration der Kulturen im europäischen Mittelalter
Das mittelalterliche Europa war keine christliche Einheitskultur, sondern geprägt von vielfältigen Prozessen des Kontakts und der Abgrenzung zwischen Kulturen, bei denen die drei monotheistischen Religionen Christentum, Judentum und Islam eine herausragende Rolle spielten. Seit 2005 erforscht das DFG-Schwerpunktprogramm "Integration und Desintegration der Kulturen im europäischen Mittelalter" die Geschichte Europas als Geschichte kultureller Differenzen. Der Band dokumentiert die Dynamiken und Erträge eines wissenschaftsorganisatorischen Experiments: Gegliedert in fächerübergreifende Arbeitsgruppen, erforschten 24 Einzelprojekte aus 14 Disziplinen Integrations- und Desintegrationsprozesse von Skandinavien bis Ägypten, von der Iberischen Halbinsel bis zu den Steppen Zentralasiens in komparativem Zugriff; sie präsentieren ihre Ergebnisse nun in Beiträgen, die von mehreren Autorinnen und Autoren gemeinsam verfasst worden sind. Dabei werden Begriffe wie "Kultur" problematisiert und schon eingeführte Konzepte wie "Integration/Desintegration", "Inklusion/Exklusion", "Hybridisierung" und "Transfer" als Instrumente transkultureller Mediävistik auf den Prüfstand gestellt. Das Ende der Laufzeit des Schwerpunktprogramms gibt zugleich Anlass, methodisch-theoretische Einsichten der gemeinsamen Forschung wie auch praktische Erfahrungen bei der transdisziplinären Zusammenarbeit zu bilanzieren
Gradient-based Optimization of Kernel-Target Alignment for Sequence Kernels Applied to Bacterial Gene Start Detection
Biological data mining using kernel methods can be improved by a task-specific choice of the kernel function. Oligo kernels for genomic sequence analysis have proven to have a high discriminative power and to provide interpretable results. Oligo kernels that consider subsequences of different lengths can be combined and param-eterized to increase their flexibility. For adapting these parameters efficiently, gradient-based optimization of the kernel-target alignment is proposed. The power of this new, general model selection procedure and the benefits of fitting kernels to problem classes are demonstrated by adapting oligo kernels for bacterial gene start detection