Evidence map›Paper›PMID 29963077›Full record

ArticleFrontiers in genetics2018

PASSPORT-seq: A Novel High-Throughput Bioassay to Functionally Test Polymorphisms in Micro-RNA Target Sites.

Joseph Ipe, Kimberly S Collins, Yangyang Hao, Hongyu Gao, Puja Bhatia, Andrea Gaedigk, Yunlong Liu, Todd C Skaar

Open access · goldAbstract read
In one paragraph

Article in Frontiers in genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.5field-weighted citation impact, top 42% 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

10 citing papers in PubMed, 12 citations in OpenAlex.

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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

8 authors at 3 institutions in 1 country.

Joseph IpeDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States.
Kimberly S CollinsDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States.
Yangyang HaoDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States.
Hongyu GaoDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States.
Puja BhatiaDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States.
Andrea GaedigkDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, MO, United States.
Yunlong LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States.
Todd C SkaarDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States.
Indiana University – Purdue University Indianapolis · USIndiana University School of MedicineChildren's Mercy Hospital · US

Funding

INDIANA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (UL1): BPCAUL1RR025761 · NCRR · INDIANA UNIVERSITY INDIANAPOLIS · PI SHEKHAR, ANANTHA · 2008 to 2011
$21.0M
Regulation of drug metabolizing enzymes by miRNAsR01GM088076 · NIGMS · INDIANA UNIVERSITY INDIANAPOLIS · PI SKAAR, TODD C. · 2009 to 2017
$3.8M
Indiana Clinical and Translational Sciences InstituteTL1TR001107 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$2.0M
Age-related changes in microRNA expression effect on drug metabolism in human liverF31GM119401 · NIGMS · INDIANA UNIVERSITY INDIANAPOLIS · PI COLLINS, KIMBERLY S. · 2016 to 2017
$40k
NCATS NIH HHS TL1 TR001107NCRR NIH HHS UL1 RR025761NIGMS NIH HHS F31 GM119401NIGMS NIH HHS R01 GM088076
6 · The paper itself

Abstract

Next-generation sequencing (NGS) studies have identified large numbers of genetic variants that are predicted to alter miRNA-mRNA interactions. We developed a novel high-throughput bioassay, PASSPORT-seq, that can functionally test in parallel 100s of these variants in miRNA binding sites (mirSNPs). The results are highly reproducible across both technical and biological replicates. The utility of the bioassay was demonstrated by testing 100 mirSNPs in HEK293, HepG2, and HeLa cells. The results of several of the variants were validated in all three cell lines using traditional individual luciferase assays. Fifty-five mirSNPs were functional in at least one of three cell lines (FDR ≤ 0.05); 11, 36, and 27 of them were functional in HEK293, HepG2, and HeLa cells, respectively. Only four of the variants were functional in all three cell lines, which demonstrates the cell-type specific effects of mirSNPs and the importance of testing the mirSNPs in multiple cell lines. Using PASSPORT-seq, we functionally tested 111 variants in the 3' UTR of 17 pharmacogenes that are predicted to alter miRNA regulation. Thirty-three of the variants tested were functional in at least one cell line.

Indexed as

3′ UTRfunctional testinggenetic variantshigh-throughput screening assaysmiRNASNP

Identifiers

PMID29963077
PMCPMC6013768
OpenAlexW2806413447

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Registered trials

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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.