Evidence map›Paper›PMID 30903145›Full record

ArticleBioinformatics (Oxford, England)2019

ORE identifies extreme expression effects enriched for rare variants.

F Richter, G E Hoffman, K B Manheimer, N Patel, A J Sharp, D McKean, S U Morton, S DePalma, J Gorham, A Kitaygorodksy and 8 more

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

Article in Bioinformatics (Oxford, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
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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

18 authors at 7 institutions in 2 countries.

F RichterGraduate School of Biomedical Sciences.
G E HoffmanIcahn Institute for Genomics and Multiscale Biology.
K B ManheimerSema4, A Mount Sinai Venture, Stamford, CT, USA.
N PatelMindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
A J SharpDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
D McKeanDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
S U MortonDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
S DePalmaDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
J GorhamDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
A KitaygorodksyDepartment of Systems Biology, Columbia University, New York, NY, USA.
G A PorterDepartment of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
A GiardiniCardiorespiratory Unit, Great Ormond Street Hospital and University College London, London, UK.
Y ShenDepartment of Systems Biology, Columbia University, New York, NY, USA.
W K ChungDepartment of Pediatrics and Medicine, Columbia University, New York, NY, USA.
J G SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
C E SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
E E SchadtIcahn Institute for Genomics and Multiscale Biology.
B D GelbDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Harvard University · USChild Health and Development Institute · USColumbia University · USSema4 (United States) · USGenomics (United Kingdom) · GBGreat Ormond Street Hospital · GBUniversity of Rochester Medical Center · US

Funding

GMKF competing renewalU24HD090743 · NICHD · BROAD INSTITUTE, INC. · PI Stacey Gabriel · 2016 to 2026
$68.3M
Administrative Coordinating Center: Cardiovascular Development and Pediatric Cardiac Genomics ConsortiaU01HL131003 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI CNOTA, JAMES, OLLBERDING, NICHOLAS J · 2016 to 2024
$54.8M
MOUNT SINAI MEDICAL SCIENTIST TRAINING PROGRAMT32GM007280 · NIGMS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BARON, MARGARET H · 1985 to 2021
$22.8M
T32 training grant in medical genetics.T32GM082773 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Laszlo Tamas Kozicz, Eva Morava-Kozicz · 2008 to 2026
$4.9M
Regulation of Cardiac Development in Health and DiseaseUM1HL098166 · NHLBI · HARVARD MEDICAL SCHOOL · PI PENNACCHIO, LEN ALEXANDER, PU, WILLIAM TSWENCHING · 2015 to 2019
$4.4M
Genetics of Hypoplastic Left Heart SyndromeUM1HL128761 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BERNSTEIN, DANIEL, SRIVASTAVA, DEEPAK · 2015 to 2019
$2.5M
The Genomic Basis of Congenital Heart Disease and Neurodevelopmental OutcomesUM1HL098147 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI NEWBURGER, JANE W., ROBERTS, AMY E · 2015 to 2019
$2.4M
Identifying and applying genetic variation relevant to clinical outcomes for individuals with congenital heart diseaseU01HL153009 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CHUNG, WENDY K, GELB, BRUCE D · 2020 to 2024
$2.3M
Genetics of conotruncal defects and associated neurodevelopmental outcomesUM1HL098123 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GELB, BRUCE D · 2015 to 2019
$2.3M
Genetics and genomics of congenital heart disease and associated neurodevelopmental abnormalitiesUM1HL098162 · NHLBI · YALE UNIVERSITY · PI BRUECKNER, MARTINA, GUPTA, ABHA RANI · 2015 to 2019
$2.2M
Bridging the Gap between Genomics and Clinical Outcomes in CHDUM1HL128711 · NHLBI · UNIVERSITY OF UTAH · PI TRISTANI-FIROUZI, MARTIN, YANDELL, MARK DOUGLAS · 2015 to 2019
$2.0M
Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC SupercomputerS10OD018522 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2014 to 2014
$1.9M
NHLBI NIH HHS U01 HL131003NHLBI NIH HHS U01 HL153009NHLBI NIH HHS UM1 HL098123NHLBI NIH HHS UM1 HL098147NHLBI NIH HHS UM1 HL098162NHLBI NIH HHS UM1 HL098166NHLBI NIH HHS UM1 HL128711NHLBI NIH HHS UM1 HL128761NICHD NIH HHS T32 HD075735NICHD NIH HHS U24 HD090743NIGMS NIH HHS T32 GM007280NIGMS NIH HHS T32 GM082773NIH HHS S10 OD018521NIH HHS S10 OD018522
6 · The paper itself

Abstract

motivationNon-coding rare variants (RVs) may contribute to Mendelian disorders but have been challenging to study due to small sample sizes, genetic heterogeneity and uncertainty about relevant non-coding features. Previous studies identified RVs associated with expression outliers, but varying outlier definitions were employed and no comprehensive open-source software was developed.

resultsWe developed Outlier-RV Enrichment (ORE) to identify biologically-meaningful non-coding RVs. We implemented ORE combining whole-genome sequencing and cardiac RNAseq from congenital heart defect patients from the Pediatric Cardiac Genomics Consortium and deceased adults from Genotype-Tissue Expression. Use of rank-based outliers maximized sensitivity while a most extreme outlier approach maximized specificity. Rarer variants had stronger associations, suggesting they are under negative selective pressure and providing a basis for investigating their contribution to Mendelian disorders. AVAILABILITY AND IMPLEMENTATION: ORE, source code, and documentation are available at https://pypi.python.org/pypi/ore under the MIT license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Indexed as

GenomicsSoftwareChildDocumentationHumansUncertaintyWhole Genome Sequencing

Identifiers

PMID30903145
PMCPMC6792115
OpenAlexW2940517989

What OpenQuestion holds

Textmetadata
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.