Pelin (Akan) Sahlén
Pelin (Akan) Sahlén
KTH Royal Institute of Technology
Our aim is to map promoter-enhancer interactions particularly in human complex disease context. We developed HiCap by combining 4-cutter Hi-C with sequence capture targeting promoters (Sahlén P et al 2015). We now improved our capture design to target promoters more efficiently with fewer amounts of probes making the method cost-effective.
Promoters are central players in regulating expression levels of genes. However it is through their interactions with distal acting enhancers, that they achieve specific patterns of expression in different cells, tissues and developmental stages. In general, regulatory mutations (e.g. those in promoters and enhancers) carry lower burdens for the fitness of individuals than those of protein-coding mutations. Indeed, around 93% of complex disease-associated variants from genome-wide association studies (GWAS) lie within noncoding sequences and 77% of those are strong candidates for enhancers (Maurano MT et al, 2012). Therefore it is of paramount importance to know the target genes of such regions to understand their functional implications in disease.
We currently apply HiCap in cardiovascular disease context to map interactions of associated regions to find their target genes. We also apply HiCap for soft-tissue sarcoma and normal samples taken from patients to identify any possible disease associanted regulatory miswiring.
Rapolas Spalinskas, Post doc
Sahlén P, Abdullayev I, Ramsköld D, Matskova L, Rilakovic N, Lötstedt B, Albert TJ, Lundeberg J, Sandberg R. Genome-wide mapping of promoter-anchored interactions with close to single-enhancer resolution. Genome Biology 2015, 16:156
Costea PI, Lundeberg J, Akan P. TagGD: fast and accurate software for DNA Tag generation and demultiplexing. PLoS One 2013;8(3):e57521
Akan P, Alexeyenko A, Costea PI, Hedberg L, Solnestam BW, Lundin S, Hällman J, Lundberg E, Uhlén M, Lundeberg J. Comprehensive analysis of the genome transcriptome and proteome landscapes of three tumor cell lines. Genome Medicine 2012 Nov 19;4(11):86
Solnestam BW, Stranneheim H, Hällman J, Käller M, Lundberg E, Lundeberg J, Akan P. Comparison of total and cytoplasmic mRNA reveals global regulation by nuclear retention and miRNAs. BMC Genomics 2012 Oct 30;13:574