EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001004373EGAEGA study EGAS00001004373Whole exome sequencing data from non-small-cell lung cancer patients receiving immunotherapy prognosisEGArestrictedImmunotherapies, Prognoses, Factors, Malignant Neoplasm, whole blood, Malignancy, Neoplasms, Prognostic, Benign Neoplasm, Benign Neoplasms, Prognostic Factors, Cancers, Factor, Tumor, Prognostic Factor., Malignant, Malignant Neoplasms, allergic reaction, Neoplasias, Mutations, Benign, sensitive, Neoplasm, Malignancies, other neoplasm, sensitivity, Neoplasia, Cancer, TumorsBiological Markers, Viral Marker, Surrogate Endpoints, Laboratory, Addresses, Biochemical, Endpoint, Measure, Tumor, Serum, composed of, Cost-Minimization, Long Term, Mutations, dmTAF[[II]]230, Techniques, Laboratory Markers, Method, Biological, Alleviating interaction, Analysis, Cost Comparison, Effect, thymus nucleic acid, me75, TFIID TAF250, Analyses, cel, Cost-Minimization Analyses, composition, cell sheath, Comparison, free, D17Mit170, T1, allergic reaction, K2p3.1, Cost Analysis, Immune, Markers, Methodological Studies, malignant neoplasm, Viral Markers, Double-Stranded DNA, Malignancies, deoxyribonucleic acids, Comparisons, DNAn, Affordabilities, Long-Term Effects, Tumors, dTAF[[II]]230, Viral, Surrogate Endpoint, frequency, lamina, TAF200, Longterm Effect, Biochemical Markers, Double-Stranded, TAFII-250, Procedure, TAF250/230, Tl3, Tl2, Biologic Marker, (Deoxyribonucleotide)n+m, TAFII250, Benign, TBAK1, Marker, desoxyribose nucleic acid, finances, PPH4, End Points, content, Exomes, salaries, Benign Neoplasms, Methodological, Immunologic, Laboratory Marker, CG17603, TAF[[II]], Methodological Study, surveillance, morbidity, Malignant Neoplasms, Taf250, Patient, Specificity and Sensitivity, Biochemical Marker, SR3-5, ds DNA, DNA, financial management, TASK-1, other neoplasm, TAF230, Cost Analyses, whole exome, d230, DNS, Procedures, (Deoxyribonucleotide)n, Effects, Clinical Markers, Clinical Marker, Neoplasms, Benign Neoplasm, dTAFII250, Cost Comparisons, EfW1, Malignant, Deoxyribonucleic acids, Surrogate End Points, Surrogate Markers, method, Deoxyribonucleic Acid, Cost Minimization Analysis, dmTAF1, Taf230, sensitive, method used in an experiment, Studies, Low, Technique, sensitivity, TAF250, Biomarker, Taf200, WES, dTAF[[II]]250, Clinical, Malignancy, Longterm, occurrence, cell, Cost Measures, layer, Affordability, Biological Marker, prevalence, Double Stranded, Measures, Taf1p, Deoxyribonucleic acid, Long-Term, financing, suppressive genetic interaction (sensu inequality), Neoplasias, Study, dTAF250, funding, Immunologic Markers, Clients, Sensitivity, Long-Term Effect, (Deoxyribonucleotide)m, TAF, Immunologic Marker, incidence, Biologic, Cancer, fees, TAF[[II]]250, Malignant Neoplasm, cou, OAT1, DNAn+1, Serum Markers, Immunotherapies., End Point, l(3)84Ab, BG:DS00004.13, compositionality, Client, Cell, Faces, Immune Marker, dTAF230, TASK, Lr, MT, Surrogate End Point, p230, Long Term Effects, Neoplasm, TAF[[II]]250/230, TFIID, ds-DNA, outbreaks, Costs and Cost Analyses, Biologic Markers, Taf[[II]]250, Costs, primary cancer, Serum Marker, TAF[[II]]230, Surrogate, Cost, Endpoints, Specificity, Cost-Minimization Analysis, TAF[II]250, patient, Cancers, Pricing, malignant tumor, endemics, Surrogate Marker, Longterm Effects, plan specification, cost, DmelCG17603, structure, sheath of cells, Desoxyribonukleinsaeure, Bra, layer of cells, epidemics, Cost Measure, Neoplasia, TAF1, Immune MarkersfalseSensitive detection of tumor mutations from blood and its application to immunotherapy prognosisCell-free DNA (cfDNA) is attractive for many applications, including cancer detection, locating, and monitoring. A fundamental task underlying these applications is the SNV calling from cfDNA, which, however, faces a new challenge, namely, the generally very low tumor content in cfDNA. Thus all existing callers fail to achieve satisfactory performance. Here we present cfSNV, a method incorporating multi-layer error suppression and hierarchical mutation calling, to address this important challenge. Furthermore, by leveraging cfDNA’s comprehensive coverage of clonal landscape, for the first time cfSNV can profile mutations even in subclones. In both simulated and real patient data, cfSNV vastly outperforms existing tools, showing tens of times increase in sensitivity in detecting mutations with low allele frequency while maintaining high precision. cfSNV can enhance the clinical utilities of cfDNA by dramatically reducing the required sequencing depth and therefore reduce the cost by magnitudes, and further make the Whole-Exome-Sequencing of cfDNA a viable option. As an example, we demonstrate that cfDNA-WES allows a new biomarker to effectively select patients for immunotherapy.2021-04-15 11:09:49EGAS000010043739606EGAD00001006096EGAC00001001569