EGAGenomicsComplete Genomics;, unspecified;https://ega-archive.org/datasets/EGAD000010001744EGA dataset EGAD00001000174EGAThe emergence of high-throughput, next-generation sequencing technologies has dramatically altered the way we assess genomes in population genetics and in cancer genomics. Currently, there are four commonly used whole-genome sequencing platforms on the market: Illumina's HiSeq2000, Life Technologies' SOLiD 4 and its completely redesigned 5500xl SOLiD, and Complete Genomics' technology. A number of earlier studies have compared a subset of those sequencing platforms or compared those platforms with Sanger sequencing, which is prohibitively expensive for whole genome studies. Here we present a detailed comparison of the performance of all currently available whole genome sequencing platforms, especially regarding their ability to call SNVs and to evenly cover the genome and specific genomic regions. Unlike earlier studies, we base our comparison on four different samples, allowing us to assess the between-sample variation of the platforms. We find a pronounced GC bias in GC-rich regions for Life Technologies' platforms, with Complete Genomics performing best here, while we see the least bias in GC-poor regions for HiSeq2000 and 5500xl. HiSeq2000 gives the most uniform coverage and displays the least sample-to-sample variation. In contrast, Complete Genomics exhibits by far the smallest fraction of bases not covered, while the SOLiD platforms reveal remarkable shortcomings, especially in covering CpG islands. When comparing the performance of the four platforms for calling SNPs, HiSeq2000 and Complete Genomics achieve the highest sensitivity, while the SOLiD platforms show the lowest false positive rate. Finally, we find that integrating sequencing data from different platforms offers the potential to combine the strengths of different technologies. In summary, our results detail the strengths and weaknesses of all four whole-genome sequencing platforms. It indicates application areas that call for a specific sequencing platform and disallow other platforms. This helps to identify the proper sequencing platform for whole genome studies with different application scopes.Coverage bias and sensitivity of variant calling for four whole-genome sequencing technologies.Rieber Nora N, Zapatka Marc M, Lasitschka Bärbel B, Jones David D, Northcott Paul P, Hutter Barbara B, Jäger Natalie N, Kool Marcel M, Taylor Michael M, Lichter Peter P, Pfister Stefan S, Wolf Stephan S, Brors Benedikt B, Eils Roland Rphapii, Scientific Bias, Fallacy, IPP2A2, Scientific, Ecological Fallacy, Epidemiologic, Truncation, igaad, StF-IT-1, Systematic Bias, Truncation Biases, Ecological Fallacies, PHAPII, group, 5730420M11Rik, Outcome Measurement Errors, Experimental, I-2PP2A, sensitive, Dm I-2, Epidemiologic Biase, I2PP2A, Errors, Ecological, Truncation Bias, sensitivity, Fallacies, SET, Ecological Biases, Bias, HLA-DR-associated protein II, ensemble, DI-2, TAF-I, I-2Dm, ipp2a2, Aggregation, Biases, Specificity, 2pp2a, CG4299, Outcome Measurement, CG10574, DmelCG4299, I-2PP1, Experimental Bias, allergic reaction, IGAAD, set, dSET/TAF-Ibeta, Outcome Measurement Error, 2610030F17Rik, TAF-IBETA, 2PP2A, DmelCG10574, Error, Specificity and Sensitivity, taf-ibeta, Aggregation Bias, Statistical Biases, Statistical Bias, dSET, dSet, Ecological Bias, Sensitivity, TAF-Ibeta, Systematic, Tech., Statistical, AA407739, Epidemiologic Biases, i2pp2a, Biasephapii, Scientific Bias, Fallacy, IPP2A2, Scientific, Ecological Fallacy, Epidemiologic, Truncation, igaad, StF-IT-1, Systematic Bias, Truncation Biases, Ecological Fallacies, PHAPII, group, 5730420M11Rik, Outcome Measurement Errors, Experimental, I-2PP2A, sensitive, Dm I-2, Epidemiologic Biase, I2PP2A, Errors, Ecological, Truncation Bias, sensitivity, Fallacies, SET, Ecological Biases, Bias, HLA-DR-associated protein II, ensemble, DI-2, TAF-I, I-2Dm, ipp2a2, Aggregation, Biases, Specificity, 2pp2a, CG4299, Outcome Measurement, CG10574, DmelCG4299, I-2PP1, Experimental Bias, allergic reaction, IGAAD, set, dSET/TAF-Ibeta, Outcome Measurement Error, 2610030F17Rik, TAF-IBETA, 2PP2A, DmelCG10574, Error, Specificity and Sensitivity, taf-ibeta, Aggregation Bias, Statistical Biases, Statistical Bias, dSET, dSet, Ecological Bias, Sensitivity, TAF-Ibeta, Systematic, Tech., Statistical, AA407739, Epidemiologic Biases, i2pp2a, BiaseFallacies, Scientific Bias, Fallacy, Ecological Biases, Bias, Scientific, Ecological Fallacy, Epidemiologic, Truncation, Aggregation, Biases, Specificity, Systematic Bias, Truncation Biases, whole genome, Outcome Measurement, Ecological Fallacies, Experimental Bias, Outcome Measurement Errors, allergic reaction, Outcome Measurement Error, Experimental, Error, Specificity and Sensitivity, Aggregation Bias, Statistical Biases, sensitive, Statistical Bias, Epidemiologic Biase, Ecological Bias, Errors, Sensitivity, Ecological, Systematic, Truncation Bias, Statistical, Epidemiologic Biases, sensitivity, Biase, Genomes.Scientific Bias, dmBest1, Military Uniform, lifespan, False, Ecological Fallacy, Neoplasms, Truncation, BEST1, Benign Neoplasm, number, Systematic Bias, Tumor, anon-WO0118547.380, Malignant, Military Uniforms, DmelCG6264, Structural, sensitive, Core Genome, Island, Epidemiologic Biase, Functional, ARB, Ecological, whole genome., Sanger sequencing, BEST1_HUMAN, sensitivity, Fallacies, Ecological Biases, Nurse Uniform, CpG Cluster, Complete, F, Whole Genome, Genomes, Malignancy, entire lifespan, entire life cycle, VMD2, Comparative Genomics, Accessory Genome, bases, Aggregation, Complete Genome Sequencing, Basen, BMD, CpG, Sequencing, dye terminator sequencing, Military, Neoplasias, Applied Biosystems SOLiD 4 System, allergic reaction, CpG Clusters, malignant neoplasm, Statistical Biases, SOLiD 4, Whole, sample, Ecological Bias, Sensitivity, Malignancies, Systematic, Epidemiologic Biases, Garments, Cancer, Tumors, Biase, RP50, Nurse, vitelliform macular dystrophy 2 (Best disease, Fallacy, CpG-Rich Islands, Genomics, Malignant Neoplasm, CG6264, Scientific, Uniform, Nucleobase, Comparative, Epidemiologic, Arts, Genome Sequencing, Truncation Biases, Functional Genomics, Ecological Fallacies, Clusters, Pangenome, results, Outcome Measurement Errors, Experimental, Nurse Uniforms, MT, Benign, Complete Genome, Base2, Base1, Neoplasm, Errors, Truncation Bias, TU15B, bestrophin), dBest1, Dbest, primary cancer, Industrial, Bias, CpG Island, Industrial Arts, best, Garment, life, dbest1, Biases, School, Specificity, Benign Neoplasms, Cancers, whole genome, Outcome Measurement, malignant tumor, sample population, Islands, CpG-Rich Island, Malignant Neoplasms, Experimental Bias, CpG Rich Islands, Outcome Measurement Error, Pan-genome, School Uniforms, Error, Cluster, Specificity and Sensitivity, Aggregation Bias, School Uniform, cardinality, Base, Statistical Bias, Uniforms, Structural Genomics, nucleobases, Population Genetics, Clothes, Statistical, BEST, Neoplasia, CpG-Rich, basefalseDATA_SET_Coverage_bias_sensitivity_of_variant_calling_for_4_WG_seq_tech - samplesDATA_SET_Coverage_bias_sensitivity_of_variant_calling_for_4_WG_seq_tech2018-05-02 09:10:04EGAD00001000174960623776689EGAC00001000219EGAS00001000274