Effects of RAF inhibitors on PI3K/AKT signalling depend on mutational status of the RAS/RAF signalling axis.

Targeted therapies within the RAS/RAF/MEK/ERK signalling axis become increasingly popular, yet cross-talk and feedbacks in the signalling network lead to unexpected effects. Here we look systematically into how inhibiting RAF and MEK with clinically relevant inhibitors result in changes in PI3K/AKT activation. We measure the signalling response using a bead-based ELISA, and use a panel of three cell lines, and isogenic cell lines that express mutant forms of the oncogenes KRAS and BRAF to interrogate the effects of the MEK and RAF inhibitors on signalling.

JAMM: a peak finder for joint analysis of NGS replicates.

Motivation: Although peak finding in next-generation sequencing (NGS) datasets has been addressed extensively, there is no consensus on how to analyze and process biological replicates. Furthermore, most peak finders do not focus on accurate determination of enrichment site widths and are not widely applicable to different types of datasets.

Results: We developed JAMM (Joint Analysis of NGS replicates via Mixture Model clustering): a peak finder that can integrate information from biological replicates, determine enrichment site widths accurately and resolve neighboring narrow peaks.

ACCUSA2: multi-purpose SNV calling enhanced by probabilistic integration of quality scores.

Summary: Direct comparisons of assembled short-read stacks are one way to identify single-nucleotide variants. Single-nucleotide variant detection is especially challenging across samples with different read depths (e.g.

High-throughput subcellular protein localization using transfected-cell arrays. Subcellular protein localization using cell arrays.

Knowledge of protein localization within the cellular environment is critical for understanding the function of the protein and its regulatory networks. Protein localization data, however, have traditionally been accumulated from single or small-scale experiments. Transfected-cell arrays (TCAs) represent a robust alternative for the high-throughput analysis of gene/protein functions in mammalian cells.

ACCUSA--accurate SNP calling on draft genomes.

Summary: Next generation sequencing technologies facilitate genome-wide analysis of several biological processes. We are interested in whole-genome genotyping. To our knowledge, none of the existing single nucleotide polymorphism (SNP) callers consider the quality of the reference genome, which is not necessary for high-quality assemblies of well-studied model organisms.