Evidence map›Paper›PMID 39271961›Full record

ArticleEMBO molecular medicine2024

CRISPR-enabled point-of-care genotyping for APOL1 genetic risk assessment.

Robert Greensmith, Isadora T Lape, Cristian V Riella, Alexander J Schubert, Jakob J Metzger, Anand S Dighe, Xiao Tan, Bernhard Hemmer, Josefine Rau, Sarah Wendlinger and 4 more

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2024. 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
–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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

14 authors.

Robert GreensmithBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID http://orcid.org/0000-0001-8142-0127
Isadora T LapeCenter for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Cristian V RiellaNephrology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
Alexander J SchubertBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID http://orcid.org/0000-0002-6907-5276
Jakob J MetzgerBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID http://orcid.org/0000-0001-6813-4425
Anand S DigheHarvard Medical School, Boston, MA, 02115, USA.
Xiao TanWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Bernhard HemmerDepartment of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Josefine RauBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID http://orcid.org/0009-0002-6319-7990
Sarah WendlingerBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Nora DiederichBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Anja SchützProtein Production & Characterization, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany.ORCID http://orcid.org/0000-0002-0606-2574
Leonardo V RiellaCenter for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. lriella@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-7636-3196
Michael M KaminskiBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. michael.kaminski@mdc-berlin.de.ORCID http://orcid.org/0000-0003-0429-7027

Funding

Deutsche Forschungsgemeinschaft (DFG) KA5060/1-1
6 · The paper itself

Abstract

Detecting genetic variants enables risk factor identification, disease screening, and initiation of preventative therapeutics. However, current methods, relying on hybridization or sequencing, are unsuitable for point-of-care settings. In contrast, CRISPR-based-diagnostics offer high sensitivity and specificity for point-of-care applications. While these methods have predominantly been used for pathogen sensing, their utilization for genotyping is limited. Here, we report a multiplexed CRISPR-based genotyping assay using LwaCas13a, PsmCas13b, and LbaCas12a, enabling the simultaneous detection of six genotypes. We applied this assay to identify genetic variants in the APOL1 gene prevalent among African Americans, which are associated with an 8-30-fold increase in the risk of developing kidney disease. Machine learning facilitated robust analysis across a multicenter clinical cohort of more than 100 patients, accurately identifying their genotypes. In addition, we optimized the readout using a multi-analyte lateral-flow assay demonstrating the ability for simplified genotype determination of clinical samples. Our CRISPR-based genotyping assay enables cost-effective point-of-care genetic variant detection due to its simplicity, versatility, and fast readout.

Indexed as

Apolipoprotein L1Point-of-Care SystemsBlack or African AmericanClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGenetic Predisposition to DiseaseGenotypeGenotyping TechniquesHumansKidney DiseasesRisk AssessmentAPOL1 protein, humanApolipoprotein L1APOL1BiomarkersCRISPR-based-genotypingDiagnosticsKidney Disease

Identifiers

PMID39271961
PMCPMC11473833

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.