Evidence map›Paper›PMID 33832433›Full record

ArticleBMC bioinformatics2021

Low-level variant calling for non-matched samples using a position-based and nucleotide-specific approach.

Jeffrey N Dudley, Celine S Hong, Marwan A Hawari, Jasmine Shwetar, Julie C Sapp, Justin Lack, Henoke Shiferaw, NISC Comparative Sequencing Program, Jennifer J Johnston, Leslie G Biesecker

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC bioinformatics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 97% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Jeffrey N DudleyNational Human Genome Research Institute, National Institutes of Health, 50 South Drive Room 5140, Bethesda, MD, 20892, USA.
Celine S HongNational Human Genome Research Institute, National Institutes of Health, 50 South Drive Room 5140, Bethesda, MD, 20892, USA. celine.hong@nih.gov.
Marwan A HawariNational Human Genome Research Institute, National Institutes of Health, 50 South Drive Room 5140, Bethesda, MD, 20892, USA.
Jasmine ShwetarNational Human Genome Research Institute, National Institutes of Health, 50 South Drive Room 5140, Bethesda, MD, 20892, USA.
Julie C SappNational Human Genome Research Institute, National Institutes of Health, 50 South Drive Room 5140, Bethesda, MD, 20892, USA.
Justin LackNIAID Collaborative Bioinformatics Resource, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Henoke ShiferawNational Human Genome Research Institute, National Institutes of Health, 50 South Drive Room 5140, Bethesda, MD, 20892, USA.
NISC Comparative Sequencing Program
Jennifer J JohnstonNational Human Genome Research Institute, National Institutes of Health, 50 South Drive Room 5140, Bethesda, MD, 20892, USA.
Leslie G BieseckerNational Human Genome Research Institute, National Institutes of Health, 50 South Drive Room 5140, Bethesda, MD, 20892, USA.
National Institutes of Health · USNational Human Genome Research Institute · US

Funding

Inter- and Intra-Species Comparative SequencingZIBHG000196 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI THOMAS, JAMES · 2009 to 2025
$177.6M
MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
Clinical and Molecular Studies of MalformationsZ01HG200328 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BIESECKER, LESLIE G · 2005 to 2008
$5.5M
Intramural NIH HHS Z01 HG200328NIGMS NIH HHS T32 GM007863NIH HHS Z01 HG200328 14NIH HHS Z01 HG200359 11
6 · The paper itself

Abstract

backgroundThe widespread use of next-generation sequencing has identified an important role for somatic mosaicism in many diseases. However, detecting low-level mosaic variants from next-generation sequencing data remains challenging.

resultsHere, we present a method for Position-Based Variant Identification (PBVI) that uses empirically-derived distributions of alternate nucleotides from a control dataset. We modeled this approach on 11 segmental overgrowth genes. We show that this method improves detection of single nucleotide mosaic variants of 0.01-0.05 variant allele fraction compared to other low-level variant callers. At depths of 600 × and 1200 ×, we observed > 85% and > 95% sensitivity, respectively. In a cohort of 26 individuals with somatic overgrowth disorders PBVI showed improved signal to noise, identifying pathogenic variants in 17 individuals.

conclusionPBVI can facilitate identification of low-level mosaic variants thus increasing the utility of next-generation sequencing data for research and diagnostic purposes.

Indexed as

High-Throughput Nucleotide SequencingNucleotidesAllelesCohort StudiesHumansSoftwareNucleotidesMosaic variantsPrediction of mosaic variantsSomatic overgrowth disorder

Identifiers

PMID33832433
PMCPMC8028235
OpenAlexW3139753494

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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.