Apr 12, 2011

A framework for variation discovery and genotyping using next-generation DNA sequencing data

Nature Genetics
Mark A DePristoMark Daly

Abstract

Recent advances in sequencing technology make it possible to comprehensively catalog genetic variation in population samples, creating a foundation for understanding human disease, ancestry and evolution. The amounts of raw data produced are prodigious, and many computational steps are required to translate this output into high-quality variant calls. We present a unified analytic framework to discover and genotype variation among multiple samples simultaneously that achieves sensitive and specific results across five sequencing technologies and three distinct, canonical experimental designs. Our process includes (i) initial read mapping; (ii) local realignment around indels; (iii) base quality score recalibration; (iv) SNP discovery and genotyping to find all potential variants; and (v) machine learning to separate true segregating variation from machine artifacts common to next-generation sequencing technologies. We here discuss the application of these tools, instantiated in the Genome Analysis Toolkit, to deep whole-genome, whole-exome capture and multi-sample low-pass (∼4×) 1000 Genomes Project datasets.

  • References39
  • Citations3234

Citations

Mentioned in this Paper

Genome
Genetics, Population
Computer Programs and Programming
Sequencing
Data Interpretation, Statistical
Massively-Parallel Sequencing
Sequence Determinations, DNA
GenBank
Single Nucleotide Polymorphism
Genome, Human

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Coronavirus Protein Structures

Deciphering and comparing the proteins of different coronaviruses forms a basis for understanding SARS-CoV-2 evolution and virus-receptor interactions. This feed follows studies analyzing the structures of coronavirus proteins, thereby revealing potential drug target sites.

DDX3X Syndrome

DDX3X syndrome is caused by a spontaneous mutation at conception that primarily affects girls due to its location on the X-chromosome. DDX3X syndrome has been linked to intellectual disabilities, seizures, autism, low muscle tone, brain abnormalities, and slower physical developments. Here is the latest research.

ALS: Stress Granules

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by cytoplasmic protein aggregates within motor neurons. TDP-43 is an ALS-linked protein that is known to regulate splicing and storage of specific mRNAs into stress granules, which have been implicated in formation of ALS protein aggregates. Here is the latest research.

Fusion Oncoproteins in Childhood Cancers

This feed explores the function of fusion oncoproteins in specific childhood cancers, including those from racial/ethnic minority and underserved groups, and to provide preclinical assessment of potential therapeutics and how fusion oncoproteins influence gene expression to perturb normal cellular programs to block lineage differentiation and development

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Mitotic-exit networks with cytokinesis

Cytokinesis is the highly regulated process that physically separates daughter and mother cells in late mitosis. The mitotic-exit network (MEN), the signalling pathway that drives mitotic exit, directly regulates cytokinesis. Discover the latest research on mitotic-exit networks with cytokinesis here.

DNA Replication Origin

DNA replication is initiated as specific gene sequences, called origins, that function to start DNA replication. Pre-replication complexes are assembled at these origins during the G1 phase of the cell cycle. These sequences allow for targeted activation or deactivation of replication. Discover the latest research on DNA replication origins here.