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Raetsch, G.

Publications and source records attributed to Raetsch, G..

2 recordsLinked to original sources

Metannot: A succinct data structure for compression of colors in dynamic de Bruijn graphs

Much of the DNA and RNA sequencing data available is in the form of high-throughput sequencing (HTS) reads and is currently unindexed by established sequence search databases. Recent succinct data structures for indexing both reference sequences and HTS data, along with associated metadata, have been based on either hashing or graph models, but many of these structures are static in nature, and thus, not well-suited as backends for dynamic databases.\n\nWe propose a parallel construction method for and novel application of the wavelet trie as a dynamic data structure for compressing and indexing graph metadata. By developing an algorithm for merging wavelet tries, we are able to construct large tries in parallel by merging smaller tries constructed concurrently from batches of data.\n\nWhen compared against general compression algorithms and those developed specifically for graph colors (VARI and Rainbowfish), our method achieves compression ratios superior to gzip and VARI, converging to compression ratios of 6.5% to 2% on data sets constructed from over 600 virus genomes.\n\nWhile marginally worse than compression by bzip2 or Rainbowfish, this structure allows for both fast extension and query. We also found that additionally encoding graph topology metadata improved compression ratios, particularly on data sets consisting of several mutually-exclusive reference genomes.\n\nIt was also observed that the compression ratio of wavelet tries grew sublinearly with the density of the annotation matrices.\n\nThis work is a significant step towards implementing a dynamic data structure for indexing large annotated sequence data sets that supports fast query and update operations. At the time of writing, no established standard tool has filled this niche.

bioinformatics

Assessing the Gene Regulatory Landscape in 1,188 Human Tumors

Cancer is characterised by somatic genetic variation, but the effect of the majority of non-coding somatic variants and the interface with the germline genome are still unknown. We analysed the whole genome and RNA-Seq data from 1,188 human cancer patients as provided by the Pan-cancer Analysis of Whole Genomes (PCAWG) project to map cis expression quantitative trait loci of somatic and germline variation and to uncover the causes of allele-specific expression patterns in human cancers. The availability of the first large-scale dataset with both whole genome and gene expression data enabled us to uncover the effects of the non-coding variation on cancer. In addition to confirming known regulatory effects, we identified novel associations between somatic variation and expression dysregulation, in particular in distal regulatory elements. Finally, we uncovered links between somatic mutational signatures and gene expression changes, including TERT and LMO2, and we explained the inherited risk factors in APOBEC-related mutational processes. This work represents the first large-scale assessment of the effects of both germline and somatic genetic variation on gene expression in cancer and creates a valuable resource cataloguing these effects.

cancer biology