Adaptive sampling brings rapid whole-genome profiling to pediatric cancer diagnosis

Children with cancer often wait through a cascade of separate molecular tests before their tumors can be classified and matched to targeted therapies. A team of Canadian researchers now reports a streamlined alternative: a single whole-genome sequencing assay built on Oxford Nanopore Technologies that uses adaptive sampling to enrich clinically relevant regions while still reading the entire genome. The study, published open access in Genome Medicine, was applied to 36 pediatric cancer and control samples and compared directly against standard clinical assays, including exome and transcriptome sequencing. The authors describe the approach, called AS-WGS, as a standardized method optimized for pediatric hematological and solid tumors that enables rapid and comprehensive molecular profiling in one assay.

The technical core of the method is a panel of 380 clinically relevant loci that the team incorporated into the adaptive sampling workflow. In their experiments, the approach delivered somatic-grade coverage averaging 172-fold in target regions while the genome overall retained an average of 18-fold coverage. That dual coverage profile is what makes the assay comprehensive rather than merely targeted: the pan-genomic reads still support genome-wide copy number analysis and methylation profiling, while the enriched regions deliver the depth needed to detect small mutations with clinical confidence.

Performance against standard clinical assays was consistent across all classes of clinically actionable alterations. The assay detected all 20 fusion genes present in the samples, identified small variants in 58 of 59 mutated genes, and captured 20 of 21 large copy number variations. Single nucleotide variants were robustly detected down to a 5 percent allelic frequency, a sensitivity the authors report as similar to clinical exome sequencing. Because the workflow is PCR-free, the same sequencing data could also support methylation-based tumor classification, providing orthogonal confirmation of hematological and solid tumor subtypes in 9 of 11 acute lymphoblastic leukemias and in 8 of 12 solid tumors.

Speed is the second pillar of the study. Nanopore sequencers stream data as they read, so the team developed an open-source bioinformatic pipeline, nf-core-oncoseq, that enables on-the-fly analysis during sequencing rather than after the run ends. Using data generated in the first 24 hours of sequencing, all clonal alterations were identified with more than 5 supporting reads: all 20 fusions and all 47 single nucleotide variants with allelic frequencies above 25 percent were detected within that window. Some alteration classes surfaced even faster, with large copy number variations and methylation-based predictions appearing within the first hour of sequencing.

For pediatric oncology, where the paper describes timely molecular classification as essential for therapeutic decision-making, the implications are considerable. Current diagnostic workflows rely on multi-step, time- and resource-intensive testing strategies, and each additional assay adds delay, cost and tissue consumption. A single assay that returns fusion status, small variant calls, copy number profiles and methylation class in parallel could compress that timeline substantially, particularly for aggressive leukemias and solid tumors where subtype informs therapy.

The authors are careful to frame the scope of their findings. The results come from a research comparison against standard clinical assays on 36 pediatric cancer and control samples, and future efforts aimed at clinical translation will be needed to establish where AS-WGS fits within the current multi-assay diagnostic landscape. Even so, the combination of adaptive sampling, real-time bioinformatics and PCR-free chemistry offers a technically coherent route toward faster and more complete genomic profiling for children with cancer.

Subject of Research: Rapid whole-genome sequencing with adaptive sampling for molecular profiling of pediatric cancers

Article Title: Accelerated and comprehensive pediatric cancer profiling using whole-genome sequencing with adaptive sampling

Article References: Geoffrion, N., Lawruk-Desjardins, C., Langlois, S., Alvarado, M. A., Dreyer, N., Lisi, V., Sagniez, M., Carrier, A. C., Richer, C., St-Hilaire, A. R., Tremblay-Dauphinais, P., Bataille, A. R., Sontag, T., Landais, S., Rouette, A., Jouan, L., Boumela, I., Khakipoor, B., Fong, S., … Lavallée, V.-P. (2026). Accelerated and comprehensive pediatric cancer profiling using whole-genome sequencing with adaptive sampling. Genome Medicine. https://doi.org/10.1186/s13073-026-01815-7

Image Credits: AI Generated

DOI: 10.1186/s13073-026-01815-7

Keywords: pediatric cancer, whole-genome sequencing, adaptive sampling, Oxford Nanopore, methylation classification, fusion genes, copy number variation, oncoseq, molecular diagnostics, leukemia, solid tumors, Genome Medicine