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Probabilistic Analysis of the Dual-Pivot Quicksort "Count" [article]

Ralph Neininger, Jasmin Straub
2017 arXiv   pre-print
Recently, Aum\"uller and Dietzfelbinger proposed a version of a dual-pivot quicksort, called "Count", which is optimal among dual-pivot versions with respect to the average number of key comparisons required. In this note we provide further probabilistic analysis of "Count". We derive an exact formula for the average number of swaps needed by "Count" as well as an asymptotic formula for the variance of the number of swaps and a limit law. Also for the number of key comparisons the asymptotic
more » ... iance and a limit law are identified. We also consider both complexity measures jointly and find their asymptotic correlation.
arXiv:1710.07505v1 fatcat:dfu32oilsfcrfgbqppr6r3ri4e

DynOmics to identify delays and co-expression patterns across time course experiments [article]

Jasmin Straube, Bevan Emma Huang, Kim-Anh Le Cao
2016 bioRxiv   pre-print
Dynamic changes in biological systems can be captured by measuring molecular expression from different levels (e.g., genes and proteins) across time. Integration of such data aims to identify molecules that show similar expression changes over time; such molecules may be co-regulated and thus involved in similar biological processes. Combining data sources presents a systematic approach to study molecular behaviour. It can compensate for missing data in one source, and can reduce false
more » ... when multiple sources highlight the same pathways. However, integrative approaches must accommodate the challenges inherent in 'omics' data, including high-dimensionality, noise, and timing differences in expression. As current methods for identification of co-expression cannot cope with this level of complexity, we developed a novel algorithm called DynOmics. DynOmics is based on the fast Fourier transform, from which the difference in expression initiation between trajectories can be estimated. This delay can then be used to realign the trajectories and identify those which show a high degree of correlation. Through extensive simulations, we demonstrate that DynOmics is efficient and accurate compared to existing approaches. We consider two case studies highlighting its application, identifying regulatory relationships across 'omics' data within an organism and for comparative gene expression analysis across organisms.
doi:10.1101/076257 fatcat:laj6ubpwpnao7ibpskgahjt3oi

ReadXplorer—visualization and analysis of mapped sequences

Rolf Hilker, Kai Bernd Stadermann, Daniel Doppmeier, Jörn Kalinowski, Jens Stoye, Jasmin Straube, Jörn Winnebald, Alexander Goesmann
2014 Bioinformatics  
Motivation: Fast algorithms and well-arranged visualizations are required for the comprehensive analysis of the ever-growing size of genomic and transcriptomic next-generation sequencing data. Results: ReadXplorer is a software offering straightforward visualization and extensive analysis functions for genomic and transcriptomic DNA sequences mapped on a reference. A unique specialty of ReadXplorer is the quality classification of the read mappings. It is incorporated in all analysis functions
more » ... nd displayed in ReadXplorer's various synchronized data viewers for (i) the reference sequence, its base coverage as (ii) normalizable plot and (iii) histogram, (iv) read alignments and (v) read pairs. ReadXplorer's analysis capability covers RNA secondary structure prediction, single nucleotide polymorphism and deletion-insertion polymorphism detection, genomic feature and general coverage analysis. Especially for RNA-Seq data, it offers differential gene expression analysis, transcription start site and operon detection as well as RPKM value and read count calculations. Furthermore, ReadXplorer can combine or superimpose coverage of different datasets. Availability and implementation: ReadXplorer is available as opensource software at http://www.readxplorer.org along with a detailed manual.
doi:10.1093/bioinformatics/btu205 pmid:24790157 pmcid:PMC4217279 fatcat:i6o7gvzc7zbmvn4cg3nbnwlvke

Characterization of the Human Papillomavirus 16 E8 Promoter

Elke Straub, Jasmin Fertey, Marcel Dreer, Thomas Iftner, Frank Stubenrauch, M. J. Imperiale
2015 Journal of Virology  
ABSTRACTPersistent infections with certain human papillomaviruses (HPV) such as HPV16 are a necessary risk factor for the development of anogenital and oropharyngeal cancers. HPV16 genomes replicate as low-copy-number plasmids in the nucleus of undifferentiated keratinocytes, which requires the viral E1 and E2 replication proteins. The HPV16 E8^E2C (or E8^E2) protein limits genome replication by repressing both viral transcription and the E1/E2-dependent DNA replication. How E8^E2C expression
more » ... regulated is not understood. Previous transcript analyses indicated that the spliced E8^E2C RNA is initiated at a promoter located in the E1 region upstream of the E8 gene. Deletion and mutational analyses of the E8 promoter region identify two conserved elements that are required for basal promoter activity in HPV-negative keratinocytes. In contrast, the transcriptional enhancer in the upstream regulatory region of HPV16 does not modulate basal E8 promoter activity. Cotransfection studies indicate that E8^E2C inhibits, whereas E2 weakly activates, the E8 promoter. Interestingly, the cotransfection of E1 and E2 induces the E8 promoter much more strongly than the major early promoter, and this is partially dependent upon binding of E2 to Brd4. Mutation of E8 promoter elements in the context of HPV16 genomes results in an increased genome copy number and elevated levels of viral early and late transcripts. In summary, the promoter responsible for the expression of E8^E2C is both positively and negatively regulated by viral and cellular factors, and this regulatory circuit may be crucial to maintain a low but constant copy number of HPV16 genomes in undifferentiated cells.IMPORTANCEHPV16 replicates in differentiating epithelia and can cause cancer. How HPV16 maintains its genome in undifferentiated cells at a low but constant level is not well understood but may be relevant for the immunological escape of HPV16 in the basal layers of the infected epithelium. This study demonstrates that the expression of the viral E8^E2C protein, which is a potent inhibitor of viral replication in undifferentiated cells, is driven by a separate promoter. The E8 promoter is both positively and negatively regulated by viral proteins and thus most likely acts as a sensor and modulator of viral copy number.
doi:10.1128/jvi.00616-15 pmid:25948744 pmcid:PMC4473580 fatcat:uu3sqy6rwfc4vb6hkcmidmcf5e

Probabilistic Analysis of the Dual-Pivot Quicksort "Count" [chapter]

Ralph Neininger, Jasmin Straub
2018 2018 Proceedings of the Fifteenth Workshop on Analytic Algorithmics and Combinatorics (ANALCO)  
Recently, Aumüller and Dietzfelbinger proposed a version of a dual-pivot quicksort, called "Count", which is optimal among dual-pivot versions with respect to the average number of key comparisons required. In this note we provide further probabilistic analysis of "Count". We derive an exact formula for the average number of swaps needed by "Count" as well as an asymptotic formula for the variance of the number of swaps and a limit law. Also for the number of key comparisons the asymptotic
more » ... nce and a limit law are identified. We also consider both complexity measures jointly and find their asymptotic correlation.
doi:10.1137/1.9781611975062.1 dblp:conf/analco/NeiningerS18 fatcat:5bcyq7kjqbehnkkubnijvdguim

DynOmics to identify delays and co-expression patterns across time course experiments

Jasmin Straube, Bevan Emma Huang, Kim-Anh Lê Cao
2017 Scientific Reports  
Dynamic changes in biological systems can be captured by measuring molecular expression from different levels (e.g., genes and proteins) across time. Integration of such data aims to identify molecules that show similar expression changes over time; such molecules may be co-regulated and thus involved in similar biological processes. Combining data sources presents a systematic approach to study molecular behaviour. It can compensate for missing data in one source, and can reduce false
more » ... when multiple sources highlight the same pathways. However, integrative approaches must accommodate the challenges inherent in 'omics' data, including high-dimensionality, noise, and timing differences in expression. As current methods for identification of co-expression cannot cope with this level of complexity, we developed a novel algorithm called DynOmics. DynOmics is based on the fast Fourier transform, from which the difference in expression initiation between trajectories can be estimated. This delay can then be used to realign the trajectories and identify those which show a high degree of correlation. Through extensive simulations, we demonstrate that DynOmics is efficient and accurate compared to existing approaches. We consider two case studies highlighting its application, identifying regulatory relationships across 'omics' data within an organism and for comparative gene expression analysis across organisms.
doi:10.1038/srep40131 pmid:28065937 pmcid:PMC5220332 fatcat:fzgfj7zvwfca5k6bxvkos6fqty

MPN: The Molecular Drivers of Disease Initiation, Progression and Transformation and their Effect on Treatment

Julian Grabek, Jasmin Straube, Megan Bywater, Steven W. Lane
2020 Cells  
Myeloproliferative neoplasms (MPNs) constitute a group of disorders identified by an overproduction of cells derived from myeloid lineage. The majority of MPNs have an identifiable driver mutation responsible for cytokine-independent proliferative signalling. The acquisition of coexisting mutations in chromatin modifiers, spliceosome complex components, DNA methylation modifiers, tumour suppressors and transcriptional regulators have been identified as major pathways for disease progression and
more » ... leukemic transformation. They also confer different sensitivities to therapeutic options. This review will explore the molecular basis of MPN pathogenesis and specifically examine the impact of coexisting mutations on disease biology and therapeutic options.
doi:10.3390/cells9081901 pmid:32823933 fatcat:k5govrwwevbpngsstnzr5iq4f4

Proteomic Analysis of the Breast Cancer Brain Metastasis Microenvironment

Priyakshi Kalita-de Croft, Jasmin Straube, Malcolm Lim, Fares Al-Ejeh, Sunil R. Lakhani, Jodi M. Saunus
2019 International Journal of Molecular Sciences  
Patients with brain-metastatic breast cancer face a bleak prognosis marked by morbidity and premature death. A deeper understanding of molecular interactions in the metastatic brain tumour microenvironment may inform the development of new therapeutic strategies. In this study, triple-negative MDA-MB-231 breast cancer cells or PBS (modelling traumatic brain injury) were stereotactically injected into the cerebral cortex of NOD/SCID mice to model metastatic colonization. Brain cells were
more » ... from five tumour-associated samples and five controls (pooled uninvolved and injured tissue) by immunoaffinity chromatography, and proteomic profiles were compared using the Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) discovery platform. Ontology and cell type biomarker enrichment analysis of the 125 differentially abundant proteins (p < 0.05) showed the changes largely represent cellular components involved in metabolic reprogramming and cell migration (min q = 4.59 × 10−5), with high-throughput PubMed text mining indicating they have been most frequently studied in the contexts of mitochondrial dysfunction, oxidative stress and autophagy. Analysis of mouse brain cell type-specific biomarkers suggested the changes were paralleled by increased proportions of microglia, mural cells and interneurons. Finally, we orthogonally validated three of the proteins in an independent xenograft cohort, and investigated their expression in craniotomy specimens from triple-negative metastatic breast cancer patients, using a combination of standard and fluorescent multiplex immunohistochemistry. This included 3-Hydroxyisobutyryl-CoA Hydrolase (HIBCH), which is integral for gluconeogenic valine catabolism in the brain, and was strongly induced in both graft-associated brain tissue (13.5-fold by SWATH-MS; p = 7.2 × 10−4), and areas of tumour-associated, reactive gliosis in human clinical samples. HIBCH was also induced in the tumour compartment, with expression frequently localized to margins and haemorrhagic areas. These observations raise the possibility that catabolism of valine is an effective adaptation in metastatic cells able to access it, and that intermediates or products could be transferred from tumour-associated glia. Overall, our findings indicate that metabolic reprogramming dominates the proteomic landscape of graft-associated brain tissue in the intracranial MDA-MB-231 xenograft model. Brain-derived metabolic provisions could represent an exploitable dependency in breast cancer brain metastases.
doi:10.3390/ijms20102524 fatcat:nwnm6nd6hfdczomkfrpgqbtkmy

Interaction of NCOR/SMRT Repressor Complexes with Papillomavirus E8^E2C Proteins Inhibits Viral Replication

Marcel Dreer, Jasmin Fertey, Saskia van de Poel, Elke Straub, Johannes Madlung, Boris Macek, Thomas Iftner, Frank Stubenrauch, Paul Francis Lambert
2016 PLoS Pathogens  
Infections with high-risk human papillomaviruses (HR-HPV) such as HPV16 and 31 can lead to ano-genital and oropharyngeal cancers and HPV types from the beta genus have been implicated in the development of non-melanoma skin cancer. HPV replicate as nuclear extrachromosomal plasmids at low copy numbers in undifferentiated cells. HPV16 and 31 mutants have indicated that these viruses express an E8^E2C protein which negatively regulates genome replication. E8^E2C shares the DNA-binding and
more » ... tion domain (E2C) with the essential viral replication activator E2 and the E8 domain replaces the replication/transcription activation domain of E2. The HR-HPV E8 domain is required for inhibiting viral transcription and the replication of the viral origin mediated by viral E1 and E2 proteins. We show now that E8^E2C also limits replication of HPV1, a mu-PV and HPV8, a beta-PV, in normal human keratinocytes. Proteomic analyses identified all NCoR/SMRT corepressor complex components (HDAC3, GPS2, NCoR, SMRT, TBL1 and TBLR1) as co-precipitating host cell proteins for HPV16 and 31 E8^E2C proteins. Co-immunoprecipitation and co-localization experiments revealed that NCoR/SMRT components interact with HPV1, 8, 16 and 31 E8^E2C proteins in an E8-dependent manner. SiRNA knock-down experiments confirm that NCoR/SMRT components are critical for both the inhibition of transcription and HPV origin replication by E8^E2C proteins. Furthermore, a dominant-negative NCoR fragment activates transcription and replication only from HPV16 and 31 wt but not from mutant genomes encoding NCoR/SMRT-binding deficient E8^E2C proteins. In summary, our data suggest that the repressive function of E8^E2C is highly conserved among HPV and that it is mediated by an E8-dependent interaction with NCoR/SMRT complexes. Our data also indicate for the first time that NCoR/SMRT complexes not only are involved in inhibiting cellular and viral transcription but also in controlling the replication of HPV origins. Human papillomaviruses (HPV) have been shown to cause ano-genital and oropharyngeal cancers and have been also implicated in non-melanoma skin cancer. HPV have a twostage replication cycle: in undifferentiated keratinocytes only a low level of genome replication without virus production can be observed whereas in differentiated keratinocytes high-level genome replication and virus production takes place. Previous studies have suggested that some HPV encode an E8^E2C protein that limits genome replication in undifferentiated cells. We now demonstrate that E8^E2C proteins from phylogenetically diverse HPV types interact with NCoR/SMRT corepressor complexes to limit viral transcription and genome replication. While NCoR/SMRT complexes are known to mediate the transcription repression functions of a wide variety of host transcription factors, this is the first evidence that NCoR/SMRT proteins also are involved in the repression of the replication of viral origins. NCoR/SMRT Corepressor Inhibits HPV Replication PLOS Pathogens |
doi:10.1371/journal.ppat.1005556 pmid:27064408 pmcid:PMC4827801 fatcat:ryrltpxbwjcfvebjbfucicdupa

Convergence of children´s depression rating scale-revised scores and clinical diagnosis in rating adolescent depressive symptomatology

Paul L. Plener, Jasmin Grieb, Nina Sproeber, Joana Straub, Alexander Schneider, Ferdinand Keller, Michael G. Koelch
2012 Mental Illness  
The Children´s Depression Rating Scale- Revised (CDRS-R) is a widely used instrument for research on depression in minors. A raw score of ≥40 has often been used as indicator of depressive symptomatology. As a validated German version of the CDRS-R has recently became available, we assessed CDRS-R raw summary scores of a video taped interview session in two different rater groups and compared them with clinical ratings of International Classification of Diseases (ICD- 10) depression diagnosis
more » ... observed by a third independent group. We found that for the German version a raw score between 35 and 40 is indicative for mild depressive symptomatology as described by the ICD-10. CDRS-R scores show potential clinical applicability to deduct levels of depression.
doi:10.4081/mi.2012.e7 pmid:25478109 pmcid:PMC4253369 fatcat:tomt5qic5jhupl6mrf2qjandya

Convergence Rates in the Probabilistic Analysis of Algorithms

Ralph Neininger, Jasmin Straub, Clemens Heuberger, Michael Drmota
2020 International Conference on Probabilistic, Combinatorial and Asymptotic Methods for the Analysis of Algorithms  
Straub 22:5 Proof.  ... 
doi:10.4230/lipics.aofa.2020.22 dblp:conf/aofa/NeiningerS20 fatcat:ellliex4czd77gtdfe6fcpw3iy

New Insights into Weather and Stroke: Influences of Specific Air Masses and Temperature Changes on Stroke Incidence

Michael Ertl, Christoph Beck, Benjamin Kühlbach, Jasmin Hartmann, Gertrud Hammel, Annette Straub, Esther Giemsa, Stefanie Seubert, Andreas Philipp, Claudia Traidl-Hoffmann, Jens Soentgen, Jucundus Jacobeit (+1 others)
2019 Cerebrovascular Diseases  
Meteorological factors seem to influence stroke incidence, however, the complex association between weather and stroke remains unclear. Possible explanations from the literature do not categorize into subdivisions of ischemic strokes, only have small patient numbers, or refer to a selection of isolated weather elements without investigating weather changes and more.
doi:10.1159/000501843 pmid:31344703 fatcat:oeb7stb5bjcuflgussyz7x35py

Interleukin-12 from CD103 + Batf3-Dependent Dendritic Cells Required for NK-Cell Suppression of Metastasis

Deepak Mittal, Dipti Vijayan, Eva M. Putz, Amelia R. Aguilera, Kate A. Markey, Jasmin Straube, Stephen Kazakoff, Stephen L. Nutt, Kazuyoshi Takeda, Geoffrey R. Hill, Nicola Waddell, Mark J. Smyth
2017 Cancer immunology research  
Several host factors may affect the spread of cancer to distant organs; however, the intrinsic role of dendritic cells (DC) in controlling metastasis is poorly described. Here, we show in several tumor models that although the growth of primary tumors in Batf3-deficient mice, which lack cross-presenting DCs, was not different from primary tumors in wild-type (WT) control mice, Batf3-deficient mice had increased experimental and spontaneous metastasis and poorer survival. The increased
more » ... was independent of CD4 þ and CD8 þ T lymphocytes, but required NK cells and IFNg. Chimeric mice in which Batf3dependent DCs uniformly lacked the capacity to produce IL12 had metastatic burdens similar to the Batf3-deficient mice, suggesting that Batf3 þ DCs were the only cell type whose IL12 production was critical for controlling metastasis. We found that IL12-YFP reporter mice, whose lungs were injected with B16F10 melanoma, had increased numbers of IL12-expressing CD103 þ DCs with enhanced CD86 expression. Bone-marrowderived DCs from WT, but not Batf3-deficient, mice activated NK cells to produce IFNg in an IL12-dependent manner and therapeutic injection of recombinant mouse IL12 decreased metastasis in both WT and Batf3-deficient mice. Analysis of TCGA datasets revealed an association between high expression of BATF3 and IRF8 and improved survival of breast cancer patients; BATF3 expression also significantly correlated with NK-cell receptor genes, IL12, and IFNG. Collectively, our findings show that IL12 from CD103 þ DCs is critical for NK cellmediated control of tumor metastasis.
doi:10.1158/2326-6066.cir-17-0341 pmid:29070650 fatcat:cggo62dq2rgbrln53mkdj27ftq

Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity

Megan J Bywater, Deborah L Burkhart, Jasmin Straube, Arianna Sabò, Vera Pendino, James E Hudson, Gregory A Quaife-Ryan, Enzo R Porrello, James Rae, Robert G Parton, Theresia R Kress, Bruno Amati (+3 others)
2020 Nature Communications  
It is unclear why some tissues are refractory to the mitogenic effects of the oncogene Myc. Here we show that Myc activation induces rapid transcriptional responses followed by proliferation in some, but not all, organs. Despite such disparities in proliferative response, Myc is bound to DNA at open elements in responsive (liver) and non-responsive (heart) tissues, but fails to induce a robust transcriptional and proliferative response in the heart. Using heart as an exemplar of a
more » ... tissue, we show that Myc-driven transcription is re-engaged in mature cardiomyocytes by elevating levels of the positive transcription elongation factor (P-TEFb), instating a large proliferative response. Hence, P-TEFb activity is a key limiting determinant of whether the heart is permissive for Myc transcriptional activation. These data provide a greater understanding of how Myc transcriptional activity is determined and indicate modification of P-TEFb levels could be utilised to drive regeneration of adult cardiomyocytes for the treatment of heart myopathies.
doi:10.1038/s41467-020-15552-x pmid:32286286 pmcid:PMC7156407 fatcat:2aecwjbcdbaedo5mxczez65sjy

Hematopoietic stem and progenitor cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia

Therese Vu, Jasmin Straube, Amy H. Porter, Megan Bywater, Axia Song, Victoria Ling, Leanne Cooper, Gabor Pali, Claudia Bruedigam, Sebastien Jacquelin, Joanne Green, Graham Magor (+11 others)
2020 Nature Communications  
The ATAC-Seq dataset performed on BM LKS four weeks after tamoxifen treatment can be accessed here: https://genome. ucsc.edu/s/JasminS/VU_2019_CDX2_ATAC.  ... 
doi:10.1038/s41467-020-16840-2 pmid:32541670 pmcid:PMC7296000 fatcat:by2b6z5tlbhynenbpei5d4hv2u
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