Evidence map›Paper›PMID 36711922›Full record

ArticlebioRxiv : the preprint server for biology2023

Integration of single-cell multiomic measurements across disease states with genetics identifies mechanisms of beta cell dysfunction in type 2 diabetes.

Gaowei Wang, Joshua Chiou, Chun Zeng, Michael Miller, Ileana Matta, Jee Yun Han, Nikita Kadakia, Mei-Lin Okino, Elisha Beebe, Medhavi Mallick and 11 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Gaowei WangDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.
Joshua ChiouDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.
Chun ZengDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.
Michael MillerCenter for Epigenomics, University of California San Diego, La Jolla CA, USA.
Ileana MattaDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.
Jee Yun HanCenter for Epigenomics, University of California San Diego, La Jolla CA, USA.
Nikita KadakiaDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.
Mei-Lin OkinoDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.
Elisha BeebeDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.
Medhavi MallickDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.
Joan Camunas-SolerDepartment of Bioengineering, Stanford University, Stanford, USA.
Theodore Dos SantosDepartment of Pharmacology, University of Alberta, Edmonton, AB, Canada.
Xiao-Qing DaiDepartment of Pharmacology, University of Alberta, Edmonton, AB, Canada.
Cara EllisDepartment of Pharmacology, University of Alberta, Edmonton, AB, Canada.
Yan HangDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA.
Seung K KimDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA.
Patrick E MacDonaldDepartment of Pharmacology, University of Alberta, Edmonton, AB, Canada.
Fouad R KandeelDepartment of Clinical Diabetes, Endocrinology & Metabolism, City of Hope, Duarte, CA, USA.
Sebastian PreisslCenter for Epigenomics, University of California San Diego, La Jolla CA, USA.
Kyle J GaultonDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.
Maike SanderDepartment of Pediatrics, University of California San Diego, La Jolla CA, USA.

Funding

Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
Penn integrated Human Pancreas procurement and Analysis ProgramUC4DK112217 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BETTS, MICHAEL R, FELDMAN, MICHAEL D · 2016 to 2020
$17.8M
Supplement to Integrated Program for Human Pancreas Procurement and AnalysisUC4DK112232 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ATKINSON, MARK A., POWERS, ALVIN C · 2016 to 2020
$8.4M
Nkx6 gene function in pancreas developmentR01DK068471 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI WORTHAM, MATTHEW · 2004 to 2024
$6.6M
Human Pancreas Analysis Program-T2DU01DK123716 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ATKINSON, MARK A., BOTTINO, RITA · 2019 to 2024
$6.6M
Functional Analysis of T2D Associated Non-coding SNPsU01DK105541 · NIDDK · LUDWIG INSTITUTE FOR CANCER RES LTD · PI FRAZER, KELLY A, REN, BING · 2015 to 2019
$4.6M
Genetic mechanisms of type 1 diabetes risk in stress-induced pancreatic isletsR01DK122607 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAULTON, KYLE JEFFRIE · 2019 to 2022
$4.4M
Linking islet cell function and identity from in vitro to in situU01DK120447 · NIDDK · UNIVERSITY OF ALBERTA · PI ARROJO E DRIGO, RAFAEL, LUNDBERG, EMMA · 2018 to 2021
$3.0M
Diabetes risk variants affecting transcription factor-regulated cellular networksR01DK114650 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAULTON, KYLE JEFFRIE · 2018 to 2022
$1.9M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK068471NIDDK NIH HHS R01 DK114650NIDDK NIH HHS R01 DK122607NIDDK NIH HHS U01 DK105541NIDDK NIH HHS U01 DK120447NIDDK NIH HHS U01 DK123716NIDDK NIH HHS UC4 DK112217NIDDK NIH HHS UC4 DK112232NIH HHS S10 OD026929
6 · The paper itself

Abstract

Altered function and gene regulation of pancreatic islet beta cells is a hallmark of type 2 diabetes (T2D), but a comprehensive understanding of mechanisms driving T2D is still missing. Here we integrate information from measurements of chromatin activity, gene expression and function in single beta cells with genetic association data to identify disease-causal gene regulatory changes in T2D. Using machine learning on chromatin accessibility data from 34 non-diabetic, pre-T2D and T2D donors, we robustly identify two transcriptionally and functionally distinct beta cell subtypes that undergo an abundance shift in T2D. Subtype-defining active chromatin is enriched for T2D risk variants, suggesting a causal contribution of subtype identity to T2D. Both subtypes exhibit activation of a stress-response transcriptional program and functional impairment in T2D, which is likely induced by the T2D-associated metabolic environment. Our findings demonstrate the power of multimodal single-cell measurements combined with machine learning for identifying mechanisms of complex diseases.

Identifiers

PMID36711922
PMCPMC9881862

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

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.