@article{Perscheid2021, author = {Perscheid, Cindy}, title = {Integrative biomarker detection on high-dimensional gene expression data sets}, series = {Briefings in bioinformatics}, volume = {22}, journal = {Briefings in bioinformatics}, number = {3}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1467-5463}, doi = {10.1093/bib/bbaa151}, pages = {18}, year = {2021}, abstract = {Gene expression data provide the expression levels of tens of thousands of genes from several hundred samples. These data are analyzed to detect biomarkers that can be of prognostic or diagnostic use. Traditionally, biomarker detection for gene expression data is the task of gene selection. The vast number of genes is reduced to a few relevant ones that achieve the best performance for the respective use case. Traditional approaches select genes based on their statistical significance in the data set. This results in issues of robustness, redundancy and true biological relevance of the selected genes. Integrative analyses typically address these shortcomings by integrating multiple data artifacts from the same objects, e.g. gene expression and methylation data. When only gene expression data are available, integrative analyses instead use curated information on biological processes from public knowledge bases. With knowledge bases providing an ever-increasing amount of curated biological knowledge, such prior knowledge approaches become more powerful. This paper provides a thorough overview on the status quo of biomarker detection on gene expression data with prior biological knowledge. We discuss current shortcomings of traditional approaches, review recent external knowledge bases, provide a classification and qualitative comparison of existing prior knowledge approaches and discuss open challenges for this kind of gene selection.}, language = {en} } @article{VanHoutTachmazidouBackmanetal.2020, author = {Van Hout, Cristopher V. and Tachmazidou, Ioanna and Backman, Joshua D. and Hoffman, Joshua D. and Liu, Daren and Pandey, Ashutosh K. and Gonzaga-Jauregui, Claudia and Khalid, Shareef and Ye, Bin and Banerjee, Nilanjana and Li, Alexander H. and O'Dushlaine, Colm and Marcketta, Anthony and Staples, Jeffrey and Schurmann, Claudia and Hawes, Alicia and Maxwell, Evan and Barnard, Leland and Lopez, Alexander and Penn, John and Habegger, Lukas and Blumenfeld, Andrew L. and Bai, Xiaodong and O'Keeffe, Sean and Yadav, Ashish and Praveen, Kavita and Jones, Marcus and Salerno, William J. and Chung, Wendy K. and Surakka, Ida and Willer, Cristen J. and Hveem, Kristian and Leader, Joseph B. and Carey, David J. and Ledbetter, David H. and Cardon, Lon and Yancopoulos, George D. and Economides, Aris and Coppola, Giovanni and Shuldiner, Alan R. and Balasubramanian, Suganthi and Cantor, Michael and Nelson, Matthew R. and Whittaker, John and Reid, Jeffrey G. and Marchini, Jonathan and Overton, John D. and Scott, Robert A. and Abecasis, Goncalo R. and Yerges-Armstrong, Laura M. and Baras, Aris}, title = {Exome sequencing and characterization of 49,960 individuals in the UK Biobank}, series = {Nature : the international weekly journal of science}, volume = {586}, journal = {Nature : the international weekly journal of science}, number = {7831}, publisher = {Macmillan Publishers Limited}, address = {London}, organization = {Regeneron Genetics Ctr}, issn = {0028-0836}, doi = {10.1038/s41586-020-2853-0}, pages = {749 -- 756}, year = {2020}, abstract = {The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world(1). Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6\% have a frequency of less than 1\%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97\%) had at least one carrier with a LOF variant, and most genes (more than 69\%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, includingPIEZO1on varicose veins,COL6A1on corneal resistance,MEPEon bone density, andIQGAP2andGMPRon blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2\% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenicBRCA1andBRCA2variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.
Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.}, language = {en} } @article{ChoiSchmidtTinnefeldetal.2019, author = {Choi, Youngeun and Schmidt, Carsten and Tinnefeld, Philip and Bald, Ilko and R{\"o}diger, Stefan}, title = {A new reporter design based on DNA origami nanostructures for quantification of short oligonucleotides using microbeads}, series = {Scientific Reports}, journal = {Scientific Reports}, number = {9}, publisher = {Macmillan Publishers Limited}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-019-41136-x}, pages = {8}, year = {2019}, abstract = {The DNA origami technique has great potential for the development of brighter and more sensitive reporters for fluorescence based detection schemes such as a microbead-based assay in diagnostic applications. The nanostructures can be programmed to include multiple dye molecules to enhance the measured signal as well as multiple probe strands to increase the binding strength of the target oligonucleotide to these nanostructures. Here we present a proof-of-concept study to quantify short oligonucleotides by developing a novel DNA origami based reporter system, combined with planar microbead assays. Analysis of the assays using the VideoScan digital imaging platform showed DNA origami to be a more suitable reporter candidate for quantification of the target oligonucleotides at lower concentrations than a conventional reporter that consists of one dye molecule attached to a single stranded DNA. Efforts have been made to conduct multiplexed analysis of different targets as well as to enhance fluorescence signals obtained from the reporters. We therefore believe that the quantification of short oligonucleotides that exist in low copy numbers is achieved in a better way with the DNA origami nanostructures as reporters.}, language = {en} }