Evidence map›Paper›PMID 42286715›Full record

ArticleGenome biology2026

Benchmarking Q40 sequencing for sensitive and efficient detection of rare genomic variants.

Shumeng Duan, Yaqing Liu, Xiaorou Guo, Zhiyin An, Ruiwen Ma, Qiaochu Chen, Yanming Xie, Qingwang Chen, Ying Yu, Lianhua Dong and 2 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Shumeng Duan *State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
Yaqing Liu *State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
Xiaorou GuoState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
Zhiyin AnState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
Ruiwen MaState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
Qiaochu ChenState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
Yanming XieState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
Qingwang ChenState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
Ying YuState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
Lianhua DongCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, 100013, China.
Leming ShiState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China. lemingshi@fudan.edu.cn.
Yuanting ZhengState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China. zhengyuanting@fudan.edu.cn.

Funding

111 Project B13016 to L.S.National Key R&D Program of China 2023YFF0613302 to Y.Y. and 2023YFF0613300 to L.D.National Key R&D Project of China 2023YFC3402501 to L.S.National Natural Science Foundation of China T2425013 to Y.Z., 32370701 to L.S., 32470692 to Y.Z., and 32170657 to L.S.Shanghai Municipal Science and Technology Major Project 2023SHZDZX02 and 2017SHZDZX01 to L.S.Shanghai Science and Technology Innovation Action Plan 24JS2840100 to Y.Z.State Key Laboratory of Genetics and Development of Complex Phenotypes SKLGE-2117 to L.S.
6 · The paper itself

Abstract

backgroundPhred quality score (Q score) is critical for sequencing accuracy, yet the impact of Q40-achieving sequencing technologies (99.99% accuracy) on detecting subtle biological variations remains unvalidated.

resultsUsing a comprehensive set of well-established DNA/RNA reference materials (Quartet, NIST-RM8398, SEQC2-HCC1395/BL, MAQC, and ERCC), we benchmarked Q40 sequencing (Element AVITI) against the conventional Q30 standard (Illumina NovaSeq 6000). Q40 reduced required sequencing depth by 33.3% while maintaining accuracy for germline variants (20 × vs. 30 ×) and somatic single-nucleotide variant/insertion-deletion (SNV/InDel) (60 × vs. 90 ×). Crucially, Q40 enhanced sensitivity for low-frequency somatic mutations (variant allele frequency, VAF ≤ 0.2) by 33.3% and sixfold higher copy number variation (CNV) detection reproducibility (60.3% vs. 10.4%) with Q40 at 30 × depth, directly reducing per-sample volumes by 33.3-60% and theoretically reducing sequencing costs by 2.2-31.7%. In addition, Q40 improved the discriminatory resolution between biological samples with 13.1% signal-to-noise ratio (SNR) enhancement.

conclusionsTaken together, our findings establish the value of Q40 sequencing as a sensitive and cost-effective method for low-frequency variant detection. While this positions it as a promising tool for precision oncology, its performance in real-world clinical applications remains to be evaluated in future studies.

Indexed as

Genetic VariationGenomicsHigh-Throughput Nucleotide SequencingSequence Analysis, DNABenchmarkingDNA Copy Number VariationsHumansINDEL MutationPolymorphism, Single NucleotideReproducibility of ResultsSensitivity and SpecificityGermline variantsLow-frequency mutationsQ scoreReference materialsRNA-seqSomatic variantsWhole-exome sequencing

Identifiers

PMID42286715
PMCPMC13483158

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.