individualnucleotideresolution

Individualnucleotideresolution is a term used in genomics to describe the ability to determine the identity of every nucleotide at single-base precision within a sample derived from a single individual. In practice, achieving this resolution means distinguishing each position in a genome, transcriptome, or epigenome with single-nucleotide accuracy and, when relevant, resolving sequence variation among cells or DNA molecules from the same individual.

Technologies associated with this level of resolution rely on high-accuracy sequencing and rigorous error management. Approaches include error-corrected or consensus sequencing methods, such as duplex sequencing, which aim to suppress technical error rates beyond standard next-generation sequencing. Long-read platforms can provide haplotype-resolved data, aiding in the reconstruction of contiguous haplotypes across complex regions. Computational methods for read alignment, variant calling, and haplotype phasing are essential to interpret data at true single-nucleotide precision. In epigenomic studies, single-nucleotide resolution also covers base-specific modifications, such as DNA methylation, where the modification status is mapped at individual bases.

Applications span clinical research and diagnostics, including detection of somatic mosaicism and low-frequency variants in cancer and inherited diseases, precise haplotyping, and accurate de novo mutation discovery. In forensics and population genetics, high-resolution data can improve individual identification and ancestry inference. Limitations include substantial costs, the need for very deep coverage, and complex data analysis requirements. Technical biases, repetitive regions, and sample quality can hinder true single-nucleotide accuracy at a genome-wide scale.

See also: single-nucleotide polymorphism, single-cell sequencing, duplex sequencing, long-read sequencing, haplotype phasing, variant calling.