Evidence map›Paper›PMID 30866806›Full record

ArticleBMC genomics2019

Linear models enable powerful differential activity analysis in massively parallel reporter assays.

Leslie Myint, Dimitrios G Avramopoulos, Loyal A Goff, Kasper D Hansen

Abstract read
In one paragraph

Article in BMC genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

44 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
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  15. Single Antisense Oligonucleotides Correct Diverse Splicing Mutations in Hotspot Exons.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

4 authors.

Leslie MyintDepartment of Mathematics, Statistics, and Computer Science, Macalester College, 1600 Grand Ave, Saint Paul, MN 55105, USA.
Dimitrios G AvramopoulosMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, USA.
Loyal A GoffMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, USA.
Kasper D HansenDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, E3527, Baltimore, MD 21212, USA. khansen@jhsph.edu.ORCID http://orcid.org/0000-0003-0086-0687

Funding

Cancer Genomics:Integrative and Scalable Solutions in R / BioconductorU24CA180996 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MORGAN, MARTIN T, WALDRON, LEVI · 2014 to 2023
$6.9M
Analysis of genomics datasets at a massive scaleR01GM121459 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI HANSEN, KASPER DANIEL · 2017 to 2021
$2.3M
National Cancer Institute (US) U24CA180996NCI NIH HHS U24 CA180996NIGMS NIH HHS R01 GM121459NIGMS NIH HHS R01GM121459
6 · The paper itself

Abstract

backgroundMassively parallel reporter assays (MPRAs) have emerged as a popular means for understanding noncoding variation in a variety of conditions. While a large number of experiments have been described in the literature, analysis typically uses ad-hoc methods. There has been little attention to comparing performance of methods across datasets.

resultsWe present the mpralm method which we show is calibrated and powerful, by analyzing its performance on multiple MPRA datasets. We show that it outperforms existing statistical methods for analysis of this data type, in the first comprehensive evaluation of statistical methods on several datasets. We investigate theoretical and real-data properties of barcode summarization methods and show an unappreciated impact of summarization method for some datasets. Finally, we use our model to conduct a power analysis for this assay and show substantial improvements in power by performing up to 6 replicates per condition, whereas sequencing depth has smaller impact; we recommend to always use at least 4 replicates. An R package is available from the Bioconductor project.

conclusionsTogether, these results inform recommendations for differential analysis, general group comparisons, and power analysis and will help improve design and analysis of MPRA experiments.

Indexed as

Genome, HumanHigh-Throughput Nucleotide SequencingHumansLinear ModelsSequence Analysis, DNASequence Analysis, RNASoftwareEnhancerMassively parallel reporter assaysStatistics

Identifiers

PMID30866806
PMCPMC6417258

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.