Sanger, F., Nicklen, S. & Coulson, A. R. DNA sequencing with chain-terminating inhibitors. Proc. Natl Acad. Sci. USA 74, 5463–5467 (1977).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).

CAS 
PubMed 

Google Scholar
 

International Human Genome Sequencing Consortium Finishing the euchromatic sequence of the human genome. Nature 431, 931–945 (2004).


Google Scholar
 

Margulies, M. et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437, 376–380 (2005).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Bentley, D. R. et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456, 53–59 (2008).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

McKernan, K. J. et al. Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding. Genome Res. 19, 1527–1541 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Ronaghi, M., Uhlén, M. & Nyrén, P. A sequencing method based on real-time pyrophosphate. Science 281, 363–365 (1998).

CAS 
PubMed 

Google Scholar
 

Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Li, R., Li, Y., Kristiansen, K. & Wang, J. SOAP: short oligonucleotide alignment program. Bioinformatics 24, 713–714 (2008).

CAS 
PubMed 

Google Scholar
 

Smith, A. D., Xuan, Z. & Zhang, M. Q. Using quality scores and longer reads improves accuracy of Solexa read mapping. BMC Bioinformatics 9, 128 (2008).

PubMed 
PubMed Central 

Google Scholar
 

Schatz, M. C. CloudBurst: highly sensitive read mapping with MapReduce. Bioinformatics 25, 1363–1369 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Krawitz, P. et al. Microindel detection in short-read sequence data. Bioinformatics 26, 722–729 (2010).

CAS 
PubMed 

Google Scholar
 

Quinlan, A. R., Stewart, D. A., Strömberg, M. P. & Marth, G. T. Pyrobayes: an improved base caller for SNP discovery in pyrosequences. Nat. Methods 5, 179–181 (2008).

CAS 
PubMed 

Google Scholar
 

Koboldt, D. C. et al. VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics 25, 2283–2285 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Gibbs, R. A. The Human Genome Project changed everything. Nat. Rev. Genet. 21, 575–576 (2020).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Hillier, L. W. et al. Whole-genome sequencing and variant discovery in C. elegans. Nat. Methods 5, 183–188 (2008).

CAS 
PubMed 

Google Scholar
 

Garber, M. et al. Closing gaps in the human genome using sequencing by synthesis. Genome Biol. 10, R60 (2009).

PubMed 
PubMed Central 

Google Scholar
 

Wu, G. D. et al. Sampling and pyrosequencing methods for characterizing bacterial communities in the human gut using 16S sequence tags. BMC Microbiol. 10, 206 (2010).

PubMed 
PubMed Central 

Google Scholar
 

Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

PubMed 

Google Scholar
 

Cheung, M. K., Au, C. H., Chu, K. H., Kwan, H. S. & Wong, C. K. Composition and genetic diversity of picoeukaryotes in subtropical coastal waters as revealed by 454 pyrosequencing. ISME J. 4, 1053–1059 (2010).

PubMed 

Google Scholar
 

Stoeck, T. et al. Multiple marker parallel tag environmental DNA sequencing reveals a highly complex eukaryotic community in marine anoxic water. Mol. Ecol. 19, 21–31 (2010).

CAS 
PubMed 

Google Scholar
 

Parchman, T. L., Geist, K. S., Grahnen, J. A., Benkman, C. W. & Buerkle, C. A. Transcriptome sequencing in an ecologically important tree species: assembly, annotation, and marker discovery. BMC Genomics 11, 180 (2010).

PubMed 
PubMed Central 

Google Scholar
 

Zhang, G. et al. Deep RNA sequencing at single base-pair resolution reveals high complexity of the rice transcriptome. Genome Res. 20, 646–654 (2010).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Weber, A. P. M., Weber, K. L., Carr, K., Wilkerson, C. & Ohlrogge, J. B. Sampling the Arabidopsis transcriptome with massively parallel pyrosequencing. Plant Physiol. 144, 32–42 (2007).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Shin, H. et al. Transcriptome analysis for caenorhabditis elegans based on novel expressed sequence tags. BMC Biol. 6, 30 (2008).

PubMed 
PubMed Central 

Google Scholar
 

Bainbridge, M. N. et al. Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics 7, 246 (2006).

PubMed 
PubMed Central 

Google Scholar
 

Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L. & Wold, B. Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat. Methods 5, 621–628 (2008).

CAS 
PubMed 

Google Scholar
 

Wheeler, D. A. et al. The complete genome of an individual by massively parallel DNA sequencing. Nature 452, 872–876 (2008).

CAS 
PubMed 

Google Scholar
 

Ley, T. J. et al. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 456, 66–72 (2008).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Hodges, E. et al. Genome-wide in situ exon capture for selective resequencing. Nat. Genet. 39, 1522–1527 (2007).

CAS 
PubMed 

Google Scholar
 

Gnirke, A. et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nat. Biotechnol. 27, 182–189 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Bainbridge, M. N. et al. Whole exome capture in solution with 3 Gbp of data. Genome Biol. 11, R62 (2010).

PubMed 
PubMed Central 

Google Scholar
 

Chen, K. et al. BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat. Methods 6, 677–681 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Rausch, T. et al. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics 28, i333–i339 (2012).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Ye, K., Schulz, M. H., Long, Q., Apweiler, R. & Ning, Z. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics 25, 2865–2871 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Selvaraj, S., Schmitt, A. D., Dixon, J. R. & Ren, B. Complete haplotype phasing of the MHC and KIR loci with targeted HaploSeq. BMC Genomics 16, 900 (2015).

PubMed 
PubMed Central 

Google Scholar
 

Mose, L. E., Wilkerson, M. D., Hayes, D. N., Perou, C. M. & Parker, J. S. ABRA: improved coding indel detection via assembly-based realignment. Bioinformatics 30, 2813–2815 (2014).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Ritz, A., Paris, P. L., Ittmann, M. M., Collins, C. & Raphael, B. J. Detection of recurrent rearrangement breakpoints from copy number data. BMC Bioinformatics 12, 114 (2011).

PubMed 
PubMed Central 

Google Scholar
 

Alexander, D. H., Novembre, J. & Lange, K. Fast model-based estimation of ancestry in unrelated individuals. Genome Res. 19, 1655–1664 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Griffith, M. et al. Optimizing cancer genome sequencing and analysis. Cell Syst. 1, 210–223 (2015).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Kim, D. & Salzberg, S. L. TopHat-Fusion: an algorithm for discovery of novel fusion transcripts. Genome Biol. 12, R72 (2011).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Wu, J. et al. SOAPfusion: a robust and effective computational fusion discovery tool for RNA-seq reads. Bioinformatics 29, 2971–2978 (2013).

CAS 
PubMed 

Google Scholar
 

Rustagi, N. et al. ITD assembler: an algorithm for internal tandem duplication discovery from short-read sequencing data. BMC Bioinformatics 17, 188 (2016).

PubMed 
PubMed Central 

Google Scholar
 

Wang, K. et al. MapSplice: accurate mapping of RNA-seq reads for splice junction discovery. Nucleic Acids Res. 38, e178 (2010).

PubMed 
PubMed Central 

Google Scholar
 

International HapMap Consortium The International Hapmap Project. Nature 426, 789–796 (2003).


Google Scholar
 

1000 Genomes Project Consortium et al. A global reference for human genetic variation. Nature 526, 68–74 (2015).


Google Scholar
 

Korbel, J. O. et al. Paired-end mapping reveals extensive structural variation in the human genome. Science 318, 420–426 (2007).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Mills, R. E. et al. Mapping copy number variation by population-scale genome sequencing. Nature 470, 59–65 (2011).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Korbel, J. O. et al. PEMer: a computational framework with simulation-based error models for inferring genomic structural variants from massive paired-end sequencing data. Genome Biol. 10, R23 (2009).

PubMed 
PubMed Central 

Google Scholar
 

Hormozdiari, F., Alkan, C., Eichler, E. E. & Sahinalp, S. C. Combinatorial algorithms for structural variation detection in high-throughput sequenced genomes. Genome Res. 19, 1270–1278 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Bamshad, M. J. et al. The centers for Mendelian genomics: a new large-scale initiative to identify the genes underlying rare Mendelian conditions. Am. J. Med. Genet. A 158A, 1523–1525 (2012).

PubMed 

Google Scholar
 

Baxter, S. M. et al. Centers for Mendelian genomics: a decade of facilitating gene discovery. Genet. Med. 24, 784–797 (2022).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Burgess, D. J. The TOPMed genomic resource for human health. Nat. Rev. Genet. 22, 200 (2021).

PubMed 

Google Scholar
 

All of Us Research Program Genomics Investigators Genomic data in the all of us research program. Nature 627, 340–346 (2024).


Google Scholar
 

Conroy, M. C. et al. UK Biobank: a globally important resource for cancer research. Br. J. Cancer 128, 519–527 (2023).

PubMed 

Google Scholar
 

Mullard, A. The UK Biobank at 20. Nat. Rev. Drug Discov. 21, 628–629 (2022).

CAS 
PubMed 

Google Scholar
 

100,000 Genomes Project Pilot Investigators et al. 100,000 genomes pilot on rare-disease diagnosis in health care — preliminary report. N. Engl. J. Med. 385, 1868–1880 (2021).


Google Scholar
 

Collins, R. L. et al. A structural variation reference for medical and population genetics. Nature 581, 444–451 (2020).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Cancer Genome Atlas Research Network et al. The cancer genome atlas pan-cancer analysis project. Nat. Genet. 45, 1113–1120 (2013).

PubMed Central 

Google Scholar
 

International Cancer Genome Consortium et al. International network of cancer genome projects. Nature 464, 993–998 (2010).


Google Scholar
 

ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium Pan-cancer analysis of whole genomes. Nature 578, 82–93 (2020).


Google Scholar
 

Gröbner, S. N. et al. The landscape of genomic alterations across childhood cancers. Nature 555, 321–327 (2018).

PubMed 

Google Scholar
 

Downing, J. R. et al. The pediatric cancer genome project. Nat. Genet. 44, 619–622 (2012).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Creasy, H. H. et al. HMPDACC: a human microbiome project multi-omic data resource. Nucleic Acids Res. 49, D734–D742 (2021).

CAS 
PubMed 

Google Scholar
 

Integrative HMP (iHMP) Research Network Consortium The Integrative Human Microbiome Project. Nature 569, 641–648 (2019).


Google Scholar
 

Waters, A. J. et al. Saturation genome editing of BAP1 functionally classifies somatic and germline variants. Nat. Genet. 56, 1434–1445 (2024).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Funk, J. S. et al. Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations. Nat. Genet. 57, 140–153 (2025).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Sahu, S. et al. Saturation genome editing-based clinical classification of BRCA2 variants. Nature 638, 538–545 (2025).

CAS 
PubMed 

Google Scholar
 

Beltran, A., Jiang, X., Shen, Y. & Lehner, B. Site-saturation mutagenesis of 500 human protein domains. Nature 637, 885–894 (2025).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Huang, H. et al. Functional evaluation and clinical classification of BRCA2 variants. Nature 638, 528–537 (2025).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Eid, J. et al. Real-time DNA sequencing from single polymerase molecules. Science 323, 133–138 (2009).

CAS 
PubMed 

Google Scholar
 

Clarke, J. et al. Continuous base identification for single-molecule nanopore DNA sequencing. Nat. Nanotechnol. 4, 265–270 (2009).

CAS 
PubMed 

Google Scholar
 

Pulcu, G. S., Mikhailova, E., Choi, L.-S. & Bayley, H. Continuous observation of the stochastic motion of an individual small-molecule walker. Nat. Nanotechnol. 10, 76–83 (2015).

CAS 
PubMed 

Google Scholar
 

Huang, S., Romero-Ruiz, M., Castell, O. K., Bayley, H. & Wallace, M. I. High-throughput optical sensing of nucleic acids in a nanopore array. Nat. Nanotechnol. 10, 986–991 (2015).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Stoddart, D., Heron, A. J., Mikhailova, E., Maglia, G. & Bayley, H. Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore. Proc. Natl Acad. Sci. USA 106, 7702–7707 (2009).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Flusberg, B. A. et al. Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat. Methods 7, 461–465 (2010).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Simpson, J. T. et al. Detecting DNA cytosine methylation using Nanopore sequencing. Nat. Methods 14, 407–410 (2017).

CAS 
PubMed 

Google Scholar
 

Rand, A. C. et al. Mapping DNA methylation with high-throughput Nanopore sequencing. Nat. Methods 14, 411–413 (2017).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Chin, C.-S. et al. Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data. Nat. Methods 10, 563–569 (2013).

CAS 
PubMed 

Google Scholar
 

Sereika, M. et al. Oxford Nanopore R10.4 long-read sequencing enables the generation of near-finished bacterial genomes from pure cultures and metagenomes without short-read or reference polishing. Nat. Methods 19, 823–826 (2022).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Park, S. Y., Faraci, G., Ward, P. M., Emerson, J. F. & Lee, H. Y. High-precision and cost-efficient sequencing for real-time COVID-19 surveillance. Sci. Rep. 11, 13669 (2021).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Quick, J. et al. Real-time, portable genome sequencing for Ebola surveillance. Nature 530, 228–232 (2016).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Sedlazeck, F. J. et al. Accurate detection of complex structural variations using single-molecule sequencing. Nat. Methods 15, 461–468 (2018).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Chaisson, M. J. P. et al. Resolving the complexity of the human genome using single-molecule sequencing. Nature 517, 608–611 (2015).

CAS 
PubMed 

Google Scholar
 

Pauper, M. et al. Long-read trio sequencing of individuals with unsolved intellectual disability. Eur. J. Hum. Genet. 29, 637–648 (2021).

CAS 
PubMed 

Google Scholar
 

Showpnil, I. A. et al. Long-read genome sequencing resolves complex genomic rearrangements in rare genetic syndromes. npj Genom. Med. 9, 66 (2024).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Rangan, A. et al. Improved characterization of complex β-globin gene cluster structural variants using long-read sequencing. J. Mol. Diagn. 23, 1732–1740 (2021).

CAS 
PubMed 

Google Scholar
 

Sano, Y. et al. Likely pathogenic structural variants in genetically unsolved patients with retinitis pigmentosa revealed by long-read sequencing. J. Med. Genet. 59, 1133–1138 (2022).

CAS 
PubMed 

Google Scholar
 

Au, C. H. et al. Rapid detection of chromosomal translocation and precise breakpoint characterization in acute myeloid leukemia by Nanopore long-read sequencing. Cancer Genet. 239, 22–25 (2019).

CAS 
PubMed 

Google Scholar
 

Nurk, S. et al. The complete sequence of a human genome. Science 376, 44–53 (2022).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Vollger, M. R. et al. Segmental duplications and their variation in a complete human genome. Science 376, eabj6965 (2022).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Altemose, N. et al. Complete genomic and epigenetic maps of human centromeres. Science 376, eabl4178 (2022).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Hitz, B. C. et al. The ENCODE uniform analysis pipelines. Preprint at Res. Sq. https://doi.org/10.21203/rs.3.rs-3111932/v1 (2023).

PubMed 
PubMed Central 

Google Scholar
 

ENCODE Project Consortium A user’s guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol. 9, e1001046 (2011).


Google Scholar
 

ENCODE Project Consortium An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).


Google Scholar
 

Macosko, E. Z. et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214 (2015).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Grindberg, R. V. et al. RNA-sequencing from single nuclei. Proc. Natl Acad. Sci. USA 110, 19802–19807 (2013).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Cai, X. et al. Single-cell, genome-wide sequencing identifies clonal somatic copy-number variation in the human brain. Cell Rep. 10, 645 (2015).

CAS 
PubMed 

Google Scholar
 

Zong, C., Lu, S., Chapman, A. R. & Xie, X. S. Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 338, 1622–1626 (2012).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Tang, F. et al. mRNA-seq whole-transcriptome analysis of a single cell. Nat. Methods 6, 377–382 (2009).

CAS 
PubMed 

Google Scholar
 

Trombetta, J. J. et al. Preparation of single-cell RNA-seq libraries for next generation sequencing. Curr. Protoc. Mol. Biol. 107, 4.22.1–4.22.17 (2014).

PubMed 

Google Scholar
 

Zhu, C., Preissl, S. & Ren, B. Single-cell multimodal omics: the power of many. Nat. Methods 17, 11–14 (2020).

CAS 
PubMed 

Google Scholar
 

Cusanovich, D. A. et al. Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing. Science 348, 910–914 (2015).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Stuart, T. & Satija, R. Integrative single-cell analysis. Nat. Rev. Genet. 20, 257–272 (2019).

CAS 
PubMed 

Google Scholar
 

Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e29 (2021).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Gohil, S. H., Iorgulescu, J. B., Braun, D. A., Keskin, D. B. & Livak, K. J. Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy. Nat. Rev. Clin. Oncol. 18, 244–256 (2021).

PubMed 

Google Scholar
 

Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495–502 (2015).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Regev, A. et al. The Human Cell Atlas. eLife 6, (2017).

Tabula Sapiens Consortium et al. The Tabula Sapiens: a multiple-organ, single-cell transcriptomic atlas of humans. Science 376, eabl4896 (2022).


Google Scholar
 

Eraslan, G. et al. Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function. Science 376, eabl4290 (2022).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Domínguez Conde, C. et al. Cross-tissue immune cell analysis reveals tissue-specific features in humans. Science 376, eabl5197 (2022).

PubMed 
PubMed Central 

Google Scholar
 

Merritt, C. R. et al. Multiplex digital spatial profiling of proteins and RNA in fixed tissue. Nat. Biotechnol. 38, 586–599 (2020).

CAS 
PubMed 

Google Scholar
 

Zollinger, D. R., Lingle, S. E., Sorg, K., Beechem, J. M. & Merritt, C. R. GeoMx RNA assay: high multiplex, digital, spatial analysis of RNA in FFPE tissue. Methods Mol. Biol. 2148, 331–345 (2020).

CAS 
PubMed 

Google Scholar
 

Kulasinghe, A., Berrell, N., Donovan, M. L. & Nilges, B. S. Spatial-omics methods and applications. Methods Mol. Biol. 2880, 101–146 (2025).

PubMed 

Google Scholar
 

Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405–424 (2015).

PubMed 
PubMed Central 

Google Scholar
 

Kernohan, K. D. & Boycott, K. M. The expanding diagnostic toolbox for rare genetic diseases. Nat. Rev. Genet. 25, 401–415 (2024).

CAS 
PubMed 

Google Scholar
 

Schuetz, R. J. et al. CAVaLRi: an algorithm for rapid identification of diagnostic germline variation. Hum. Mutat. 2024, 6411444 (2024).

PubMed 
PubMed Central 

Google Scholar
 

Kamat, M. A. et al. PhenoScanner V2: an expanded tool for searching human genotype–phenotype associations. Bioinformatics 35, 4851–4853 (2019).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Slavotinek, A. et al. Predicting genes from phenotypes using Human Phenotype Ontology (HPO) terms. Hum. Genet. 141, 1749–1760 (2022).

CAS 
PubMed 

Google Scholar
 

Stark, Z. & Scott, R. H. Genomic newborn screening for rare diseases. Nat. Rev. Genet. 24, 755–766 (2023).

CAS 
PubMed 

Google Scholar
 

Kingsmore, S. F. et al. A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases. Am. J. Hum. Genet. 109, 1605–1619 (2022).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Dimmock, D. et al. Project baby bear: rapid precision care incorporating rWGS in 5 California children’s hospitals demonstrates improved clinical outcomes and reduced costs of care. Am. J. Hum. Genet. 108, 1231–1238 (2021).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Köhler, S. et al. The Human Phenotype Ontology in 2021. Nucleic Acids Res. 49, D1207–D1217 (2021).

PubMed 

Google Scholar
 

Wanders, R. J. A. et al. Translational metabolism: a multidisciplinary approach towards precision diagnosis of inborn errors of metabolism in the omics era. J. Inherit. Metab. Dis. 42, 197–208 (2019).

PubMed 

Google Scholar
 

Dragojlovic, N. et al. The cost and diagnostic yield of exome sequencing for children with suspected genetic disorders: a benchmarking study. Genet. Med. 20, 1013–1021 (2018).

PubMed 

Google Scholar
 

Tarailo-Graovac, M. et al. Exome sequencing and the management of neurometabolic disorders. N. Engl. J. Med. 374, 2246–2255 (2016).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Lunke, S. et al. Integrated multi-omics for rapid rare disease diagnosis on a national scale. Nat. Med. 29, 1681–1691 (2023).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Landrum, M. J. et al. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 42, D980–D985 (2014).

CAS 
PubMed 

Google Scholar
 

Rehm, H. L. et al. ClinGen — the clinical genome resource. N. Engl. J. Med. 372, 2235–2242 (2015).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Boycott, K. M., Azzariti, D. R., Hamosh, A. & Rehm, H. L. Seven years since the launch of the matchmaker exchange: the evolution of genomic matchmaking. Hum. Mutat. 43, 659–667 (2022).

CAS 
PubMed 

Google Scholar
 

Vollger, M. R. et al. Synchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition. Nat. Genet. 57, 469–479 (2025).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Gorzynski, J. E. et al. Ultrarapid Nanopore genome sequencing in a critical care setting. N. Engl. J. Med. 386, 700–702 (2022).

PubMed 

Google Scholar
 

Cheng, D. T. et al. Memorial Sloan Kettering-integrated mutation profiling of actionable cancer targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J. Mol. Diagn. 17, 251–264 (2015).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Suehnholz, S. P. et al. Quantifying the expanding landscape of clinical actionability for patients with cancer. Cancer Discov. 14, 49–65 (2024).

CAS 
PubMed 

Google Scholar
 

Mechahougui, H., Gutmans, J., Colarusso, G., Gouasmi, R. & Friedlaender, A. Advances in personalized oncology. Cancers 16, 2862 (2024).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Edsjö, A. et al. Current and emerging sequencing-based tools for precision cancer medicine. Mol. Asp. Med. 96, 101250 (2024).


Google Scholar
 

Steen, C. B., Liu, C. L., Alizadeh, A. A. & Newman, A. M. Profiling cell type abundance and expression in bulk tissues with CIBERSORTx. Methods Mol. Biol. 2117, 135–157 (2020).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Li, T. et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 48, W509–W514 (2020).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Ho, H.-Y., Chung, K.-S. K., Kan, C.-M. & Wong, S.-C. C. Liquid biopsy in the clinical management of cancers. Int. J. Mol. Sci. 25, 8594 (2024).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Mazzone, P. J. et al. Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection. Cancer Discov. 14, 2224–2242 (2024).

PubMed 
PubMed Central 

Google Scholar
 

Wong, D. et al. Early cancer detection in Li-Fraumeni syndrome with cell-free DNA. Cancer Discov. 14, 104–119 (2024).

CAS 
PubMed 

Google Scholar
 

van der Pol, Y. et al. Real-time analysis of the cancer genome and fragmentome from plasma and urine cell-free DNA using nanopore sequencing. EMBO Mol. Med. 15, e17282 (2023).

PubMed 
PubMed Central 

Google Scholar
 

Capper, D. et al. DNA methylation-based classification of central nervous system tumours. Nature 555, 469–474 (2018).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Djirackor, L. et al. Intraoperative DNA methylation classification of brain tumors impacts neurosurgical strategy. Neurooncol Adv. 3, vdab149 (2021).

PubMed 
PubMed Central 

Google Scholar
 

Vermeulen, C. et al. Ultra-fast deep-learned CNS tumour classification during surgery. Nature 622, 842–849 (2023).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

O’Neill, K. et al. Long-read sequencing of an advanced cancer cohort resolves rearrangements, unravels haplotypes, and reveals methylation landscapes. Cell Genom. 4, 100674 (2024).

PubMed 
PubMed Central 

Google Scholar
 

Bedrosian, T. A. et al. Detection of brain somatic variation in epilepsy-associated developmental lesions. Epilepsia 63, 1981–1997 (2022).

CAS 
PubMed 

Google Scholar
 

Miller, K. E. et al. Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy. Nat. Genet. 55, 1920–1928 (2023).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Miller, K. E. et al. Somatic mosaicism correlates with clinical findings in epilepsy brain tissue. Neurol. Genet. 6, e460 (2020).

PubMed 
PubMed Central 

Google Scholar
 

Koboldt, D. C. et al. PTEN somatic mutations contribute to spectrum of cerebral overgrowth. Brain 144, 2971–2978 (2021).

PubMed 
PubMed Central 

Google Scholar
 

Cottrell, C. E. et al. Somatic PIK3R1 variation as a cause of vascular malformations and overgrowth. Genet. Med. 23, 1882–1888 (2021).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Siegel, D. H. et al. Analyzing the genetic spectrum of vascular anomalies with overgrowth via cancer genomics. J. Invest. Dermatol. 138, 957–967 (2018).

CAS 
PubMed 

Google Scholar
 

Irtyuga, O. et al. The role of NOTCH pathway genes in the inherited susceptibility to aortic stenosis. J. Cardiovasc. Dev. Dis. 11, 226 (2024).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Usoltsev, D. et al. Complex trait susceptibilities and population diversity in a sample of 4,145 Russians. Nat. Commun. 15, 6212 (2024).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Skitchenko, R. et al. CR1 variants contribute to FSGS susceptibility across multiple populations. iScience 28, 112234 (2025).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Bocher, O., Willer, C. J. & Zeggini, E. Unravelling the genetic architecture of human complex traits through whole genome sequencing. Nat. Commun. 14, 3520 (2023).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Artomov, M., Loboda, A. A., Artyomov, M. N. & Daly, M. J. Public platform with 39,472 exome control samples enables association studies without genotype sharing. Nat. Genet. 56, 327–335 (2024).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Khera, A. V. et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat. Genet. 50, 1219–1224 (2018).

CAS 
PubMed 
PubMed Central 

Google Scholar
 

Malhotra, Y. et al. Advancements in protein structure prediction: a comparative overview of AlphaFold and its derivatives. Comput. Biol. Med. 188, 109842 (2025).

CAS 
PubMed 

Google Scholar
 

Collins, R. L. & Talkowski, M. E. Diversity and consequences of structural variation in the human genome. Nat. Rev. Genet. 26, 443–462 (2025).

CAS 
PubMed 

Google Scholar
 

Sedlazeck, F. J. et al. Piercing the dark matter: bioinformatics of long-range sequencing and mapping. Nat. Rev. Genet. 19, 329–346 (2018).

CAS 
PubMed 

Google Scholar