Biology subjects

Bernd Klaus

Publications and source records attributed to Bernd Klaus.

3 recordsLinked to original sources

bioRxiv2015

Data-driven hypothesis weighting increases detection power in multiple testing

Hypothesis weighting is a powerful approach for improving the power of data analyses that employ multiple testing. However, in general it is not evident how to choose the weights. We describe IHW, a method for data-driven hypothesis weighting that makes use of informative covariates that are independent of the test statistic under the null, but informative of each tests power or prior probability of the null hypothesis. Covariates can be continuous or categorical and need not fulfill any particular assumptions. The method increases statistical power in applications while controlling the false discovery rate (FDR) and produces additional insight by revealing the covariate-weight relationship. Independent hypothesis weighting is a practical approach to discovery of associations in large datasets.

Bioinformatics↗

bioRxiv2015

Landscape and dynamics of transcription initiation in the malaria parasite Plasmodium falciparum

The lack of a comprehensive map of transcription start sites (TSS) across the highly AT-rich genome of P. falciparum has hindered progress towards deciphering the molecular mechanisms that underly the timely regulation of gene expression in this malaria parasite. Using high-throughput sequencing technologies, we generated a comprehensive atlas of transcription initiation events at single nucleotide-resolution during the parasite intra-erythrocytic developmental cycle. This detailed analysis of TSS usage enabled us to define architectural features of plasmodial promoters. We demonstrate that TSS selection and strength are constrained by local nucleotide composition. Furthermore, we provide evidence for coordinate and stage-specific TSS usage from distinct sites within the same transcriptional unit, thereby producing transcript isoforms, a subset of which are developmentally regulated. This work offers a framework for further investigations into the interactions between genomic sequences and regulatory factors governing the complex transcriptional program of this major human pathogen.

Genomics↗

bioRxiv2014

Neural lineage induction reveals multi-scale dynamics of 3D chromatin organization

Regulation of gene expression underlies cell identity. Chromatin structure and gene activity are linked at multiple levels, via positioning of genomic loci to transcriptionally permissive or repressive environments and by connecting cis-regulatory elements such as promoters and enhancers. However, the genome-wide dynamics of these processes during cell differentiation has not been characterized. Using tethered chromatin conformation capture (TCC) sequencing we determined global three-dimensional chromatin structures in mouse embryonic stem (ES) and neural stem (NS) cell derivatives. We found that changes in the propensity of genomic regions to form inter-chromosomal contacts are pervasive in neural induction and are associated with the regulation of gene expression. Moreover, we found a pronounced contribution of euchromatic domains to the intra-chromosomal interaction network of pluripotent cells, indicating the existence of an ES cell-specific mode of chromatin organization. Mapping of promoter-enhancer interactions in pluripotent and differentiated cells revealed that spatial proximity without enhancer element activity is a common architectural feature in cells undergoing early developmental changes. Activity-independent formation of higher-order contacts between cis-regulatory elements, predominant at complex loci, may thus provide an additional layer of transcriptional control.

Molecular Biology↗