Evidence map›Paper›PMID 31159795›Full record

ArticleBMC medical genomics2019

Targeted next generation sequencing as a tool for precision medicine.

Markus Gulilat, Tyler Lamb, Wendy A Teft, Jian Wang, Jacqueline S Dron, John F Robinson, Rommel G Tirona, Robert A Hegele, Richard B Kim, Ute I Schwarz

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

Article in BMC medical genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
10.1field-weighted citation impact, top 1% 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

42 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article
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 1 institution in 1 country.

Markus GulilatDivision of Clinical Pharmacology, Department of Medicine, Western University, London Health Sciences Centre - University Hospital, 339 Windermere Road, London, ON, N6A 5A5, Canada.
Tyler LambDepartment of Physiology and Pharmacology, Western University, Medical Sciences Building, Room 216, London, ON, N6A 5C1, Canada.
Wendy A TeftDivision of Clinical Pharmacology, Department of Medicine, Western University, London Health Sciences Centre - University Hospital, 339 Windermere Road, London, ON, N6A 5A5, Canada.
Jian WangRobarts Research Institute, Western University, 1151 Richmond St. N, London, ON, N6A 5B7, Canada.
Jacqueline S DronRobarts Research Institute, Western University, 1151 Richmond St. N, London, ON, N6A 5B7, Canada.
John F RobinsonRobarts Research Institute, Western University, 1151 Richmond St. N, London, ON, N6A 5B7, Canada.
Rommel G TironaDivision of Clinical Pharmacology, Department of Medicine, Western University, London Health Sciences Centre - University Hospital, 339 Windermere Road, London, ON, N6A 5A5, Canada.
Robert A HegeleRobarts Research Institute, Western University, 1151 Richmond St. N, London, ON, N6A 5B7, Canada.
Richard B KimDivision of Clinical Pharmacology, Department of Medicine, Western University, London Health Sciences Centre - University Hospital, 339 Windermere Road, London, ON, N6A 5A5, Canada.
Ute I SchwarzDivision of Clinical Pharmacology, Department of Medicine, Western University, London Health Sciences Centre - University Hospital, 339 Windermere Road, London, ON, N6A 5A5, Canada. ute.schwarz@lhsc.on.ca.ORCID 0000-0003-1569-1580
Western University · CA

Funding

CIHR FRN-117588
6 · The paper itself

Abstract

backgroundTargeted next-generation sequencing (NGS) enables rapid identification of common and rare genetic variation. The detection of variants contributing to therapeutic drug response or adverse effects is essential for implementation of individualized pharmacotherapy. Successful application of short-read based NGS to pharmacogenes with high sequence homology, nearby pseudogenes and complex structure has been previously shown despite anticipated technical challenges. However, little is known regarding the utility of such panels to detect copy number variation (CNV) in the highly polymorphic cytochrome P450 (CYP) 2D6 gene, or to identify the promoter (TA)

methodsA panel of capture probes was generated to assess 422 kb of total coding region in 100 pharmacogenes. NGS was carried out in 235 subjects, and sequencing performance and accuracy of variant discovery validated in clinically relevant pharmacogenes. CYP2D6 CNV was determined using the bioinformatics tool CNV caller (VarSeq). Identified SNVs were assessed in terms of population allele frequency and predicted functional effects through in silico algorithms.

resultsAdequate performance of the PGxSeq panel was demonstrated with a depth-of-coverage (DOC) ≥ 20× for at least 94% of the target sequence. We showed accurate detection of 39 clinically relevant gene variants compared to standard genotyping techniques (99.9% concordance), including CYP2D6 CNV and UGT1A1*28. Allele frequency of rare or novel variants and predicted function in 235 subjects mirrored findings from large genomic datasets. A large proportion of patients (78%, 183 out of 235) were identified as homozygous carriers of at least one variant necessitating altered pharmacotherapy.

conclusionsPGxSeq can serve as a comprehensive, rapid, and reliable approach for the detection of common and novel SNVs in pharmacogenes benefiting the emerging field of precision medicine.

Indexed as

High-Throughput Nucleotide SequencingAdultChildComputer SimulationCytochrome P-450 CYP2D6DNA Copy Number VariationsGlucuronosyltransferaseHumansMolecular Sequence AnnotationPrecision MedicineUGT1A1 EnzymeCytochrome P-450 CYP2D6GlucuronosyltransferaseUGT1A1 EnzymeCopy number variationIn silico predictionNext generation sequencingPharmacogenesTargeted exome sequencing

Identifiers

PMID31159795
PMCPMC6547602
OpenAlexW2948503358

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.