A Hitchhiker's Guide to long-read genomic analysis

Genome Research, Год журнала: 2025, Номер 35(4), С. 545 - 558

Опубликована: Апрель 1, 2025

Over the past decade, long-read sequencing has evolved into a pivotal technology for uncovering hidden and complex regions of genome. Significant cost efficiency, scalability, accuracy advancements have driven this evolution. Concurrently, novel analytical methods emerged to harness full potential long reads. These enabled milestones such as first fully completed human genome, enhanced identification understanding genomic variants, deeper insights interplay between epigenetics variation. This mini-review provides comprehensive overview latest developments in DNA analysis, encompassing reference-based de novo assembly approaches. We explore entire workflow, from initial data processing variant calling annotation, focusing on how these improve our ability interpret wide array variants. Additionally, we discuss current challenges, limitations, future directions field, offering detailed examination state-of-the-art bioinformatics sequencing.

Язык: Английский

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Evolution of genome-wide methylation profiling technologies

Genome Research, Год журнала: 2025, Номер 35(4), С. 572 - 582

Опубликована: Апрель 1, 2025

In this mini-review, we explore the advancements in genome-wide DNA methylation profiling, tracing evolution from traditional methods such as arrays and whole-genome bisulfite sequencing to cutting-edge single-molecule profiling enabled by long-read (LRS) technologies. We highlight how LRS is transforming clinical translational research, particularly its ability simultaneously measure genetic epigenetic information, providing a more comprehensive understanding of complex disease mechanisms. discuss current challenges future directions field, emphasizing need for innovative computational tools robust, reproducible approaches fully harness capabilities molecular diagnostics.

Язык: Английский

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Fc gamma receptors: Their evolution, genomic architecture, genetic variation, and impact on human disease

Immunological Reviews, Год журнала: 2024, Номер unknown

Опубликована: Сен. 30, 2024

Summary Fc gamma receptors (FcγRs) are a family of that bind IgG antibodies and interface at the junction humoral innate immunity. Precise regulation receptor expression provides necessary balance to achieve healthy immune homeostasis by establishing an appropriate threshold limit autoimmunity but respond effectively infection. The underlying genetics FCGR gene central achieving this regulating affinity for IgG, signaling efficacy, expression. locus was duplicated during evolution, retaining very high homology resulting in genomic region is technically difficult study. Here, we review recent evolution mammals, its complexity variation through copy number single‐nucleotide polymorphism, impact these on disease incidence, resolution, therapeutic antibody efficacy. We also discuss progress limitations current approaches study emphasize how new genomics technologies will likely resolve much confusion field. This lead definitive conclusions genetic within function disease.

Язык: Английский

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Leveraging the power of long reads for targeted sequencing

Genome Research, Год журнала: 2024, Номер 34(11), С. 1701 - 1718

Опубликована: Ноя. 1, 2024

Long-read sequencing technologies have improved the contiguity and, as a result, quality of genome assemblies by generating reads long enough to span and resolve complex or repetitive regions genome. Several groups shown power in detecting thousands genomic epigenomic features that were previously missed short-read approaches. While these studies demonstrate how can help genome, they also highlight throughput coverage requirements needed accurately variant alleles across large populations using platforms. At time this review, whole-genome long-read is more expensive than on highest instruments; thus, achieving sufficient detect low-frequency variants (such somatic variation) heterogenous samples remains challenging. Targeted sequencing, other hand, provides depth necessary heterogeneous populations. Here, we review currently used recently developed targeted strategies leverage existing increase resolution with which look at nucleic acids variety biological contexts.

Язык: Английский

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Comprehensive Analysis of the Genetic Variation in the LPA Gene from Short-Read Sequencing

BioMed, Год журнала: 2024, Номер 4(2), С. 156 - 170

Опубликована: Июнь 4, 2024

Lipoprotein (a) (Lp(a)) is a risk factor for cardiovascular diseases and mainly regulated by the complex LPA gene. We investigated types of variation in gene their predictive performance on Lp(a) concentration. determined Kringle IV-type 2 (KIV-2) copy number (CN) using DRAGEN Caller (DLC) read depth-based CN estimator 8351 short-read whole genome sequencing samples from GENESIS-HD study. The pentanucleotide repeat promoter region was genotyped with GangSTR ExpansionHunter. concentration available 4861 population-based subjects. Predictive random forests. agreement KIV-2 between two specialized callers high (r = 0.9966; 95% confidence interval [CI] 0.9965–0.9968). Allele-specific could be 47.0% subjects DLC. can better predicted allele-specific than total CN. Two single nucleotide variants, 4925G>A rs41272114C>T, further improved prediction. genetically analyzed excellent different callers. more important predicting

Язык: Английский

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Methods to investigate somatic structural variants in synucleinopathies

Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 75 - 100

Опубликована: Окт. 1, 2024

Язык: Английский

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