In one paragraphArticle in Circulation, 2026. 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
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 registryThe 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 literatureWho cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
16 authors.
Phillip J Zhou *Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA (P.J.Z., M.V., T.Y., Q.V.P., F.V., A.T., C.A.C., R.I.S.).
Minja Velimirovic *Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA (P.J.Z., M.V., T.Y., Q.V.P., F.V., A.T., C.A.C., R.I.S.).ORCID 0000-0001-5221-6194 Tian YuDepartment of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA (P.J.Z., M.V., T.Y., Q.V.P., F.V., A.T., C.A.C., R.I.S.).ORCID 0000-0001-9447-4458 Vojislav GligorovskiLaboratory of the Physics of Biological Systems, Institute of Physics, École Polytechnique Fédérale de Lausanne, Switzerland (V.G.).ORCID 0000-0002-1804-8913 Nicolas MathisInstitute of Pharmacology and Toxicology, University of Zurich, Switzerland (N.M., G.S.).ORCID 0000-0002-4051-8344 Jing ZhaoTranslational Neuroscience Center, Boston Children's Hospital, MA (J.Z.).
Quang Vinh PhanDepartment of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA (P.J.Z., M.V., T.Y., Q.V.P., F.V., A.T., C.A.C., R.I.S.).ORCID 0000-0002-0406-5085 Felicitas VogdDepartment of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA (P.J.Z., M.V., T.Y., Q.V.P., F.V., A.T., C.A.C., R.I.S.).ORCID 0009-0007-3892-4961 Jayoung RyuMolecular Pathology Unit, Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston (J.R., L.P.).ORCID 0000-0001-8710-8898 Qisheng PanSchool of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia (Q.P., D.B.A.).
Atharva TyagiDepartment of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA (P.J.Z., M.V., T.Y., Q.V.P., F.V., A.T., C.A.C., R.I.S.).
David B AscherSchool of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia (Q.P., D.B.A.).ORCID 0000-0003-2948-2413 Gerald SchwankInstitute of Pharmacology and Toxicology, University of Zurich, Switzerland (N.M., G.S.).ORCID 0000-0003-0767-2953 Luca PinelloMolecular Pathology Unit, Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston (J.R., L.P.).ORCID 0000-0003-1109-3823 Christopher A CassaDepartment of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA (P.J.Z., M.V., T.Y., Q.V.P., F.V., A.T., C.A.C., R.I.S.).ORCID 0000-0002-5771-9177 Richard I SherwoodDepartment of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA (P.J.Z., M.V., T.Y., Q.V.P., F.V., A.T., C.A.C., R.I.S.).ORCID 0000-0001-7427-7713 Funding
Comprehensive characterization of variants underlying heart and blood diseases with CRISPR base editingUM1HG012010 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel Evan Bauer, Luca Pinello · 2021 to 2026
$10.4MHigh-throughput investigation of human genetic variants affecting cholesterol uptake and effluxR01HL164409 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SHERWOOD, RICHARD I · 2022 to 2025
$3.1MDevelopment of potent and predictable Cas9 gene activation tools through high-throughput screeningR01GM143249 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI SHERWOOD, RICHARD I · 2022 to 2024
$1.3MIntegrative computational-experimental approaches to stratify monogenic disease riskR56HG012681 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI CASSA, CHRISTOPHER, SHERWOOD, RICHARD I · 2023 to 2023
$300kNHGRI NIH HHS R56 HG012681NHGRI NIH HHS UM1 HG012010NHLBI NIH HHS R01 HL164409NIGMS NIH HHS R01 GM143249
6 · The paper itselfAbstract
backgroundInherited variants in the LDL (low-density lipoprotein) receptor (
methodsWe developed the first activity-normalized prime editing screening pipeline to measure the impact of 5184
resultsWe show that prime editing of the reporter construct correlates with endogenous variant installation frequency, validating the activity normalization approach. The resulting scores capture a continuous spectrum of functional effects, robustly separate pathogenic versus benign ClinVar variants, and show concordance with LDL-C levels in UK Biobank participants. We calibrate functional evidence strengths to the ACMG/AMP variant interpretation framework, enabling integration into a clinical variant classification workflow. By combining functional, computational, population, and contextual evidence, 322 of 434
conclusionsAltogether, activity-normalized prime editing provides a scalable framework for
Indexed as
CRISPR screeningfamilial hypercholesterolemiaLDL-cholesterolmutation scanningprime editingvariant interpretation
Identifiers
PMID42677454
PMCPMC13536972
What OpenQuestion holds
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