Evidence map›Paper›PMID 38562723›Full record

ArticlemedRxiv : the preprint server for health sciences2024

Closing the gap: Solving complex medically relevant genes at scale.

Medhat Mahmoud, John Harting, Holly Corbitt, Xiao Chen, Shalini N Jhangiani, Harsha Doddapaneni, Qingchang Meng, Tina Han, Christine Lambert, Siyuan Zhang and 17 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

27 authors.

Medhat MahmoudBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.ORCID 0000-0002-2553-4231
John HartingPacific Biosciences, Menlo Park, California, USA.
Holly CorbittTwist Bioscience, South San Francisco, USA.
Xiao ChenPacific Biosciences, Menlo Park, California, USA.
Shalini N JhangianiBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.
Harsha DoddapaneniBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.
Qingchang MengBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.
Tina HanTwist Bioscience, South San Francisco, USA.
Christine LambertPacific Biosciences, Menlo Park, California, USA.
Siyuan ZhangPacific Biosciences, Menlo Park, California, USA.
Primo BaybayanPacific Biosciences, Menlo Park, California, USA.
Geoff HennoPacific Biosciences, Menlo Park, California, USA.
Hua ShenBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.
Jianhong HuBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.
Yi HanBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.
Casey RieglerTwist Bioscience, South San Francisco, USA.
Ginger MetcalfBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.ORCID 0000-0002-8316-0071
Geoff HennoPacific Biosciences, Menlo Park, California, USA.
Ivan K ChinnDepartment of Pediatrics, Section of Immunology Allergy and Rheumatology, Center for Human Immunobiology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, USA.
Michael A EberlePacific Biosciences, Menlo Park, California, USA.ORCID 0000-0001-8965-1253
Sarah KinganPacific Biosciences, Menlo Park, California, USA.
Tim FarinholtTwist Bioscience, South San Francisco, USA.
Claudia M B CarvalhoPacific Northwest Research Institute, Seattle, USA.
Richard A GibbsBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.
Zev KronenbergPacific Biosciences, Menlo Park, California, USA.ORCID 0000-0002-7627-9808
Donna MuznyBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.
Fritz J SedlazeckBaylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, USA.ORCID 0000-0001-6040-2691

Funding

Frequency of variants of unknown significance by ancestry groups in the All of Us Research Program cohortU01HG011758 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI RICHARD A GIBBS, JAMES R. LUPSKI · 2021 to 2026
$13.8M
Shared Sequel II Systems at BCM HGSCS10OD028587 · OD · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2020 to 2020
$508k
NHGRI NIH HHS U01 HG011758NIH HHS S10 OD028587
6 · The paper itself

Abstract

Comprehending the mechanism behind human diseases with an established heritable component represents the forefront of personalized medicine. Nevertheless, numerous medically important genes are inaccurately represented in short-read sequencing data analysis due to their complexity and repetitiveness or the so-called 'dark regions' of the human genome. The advent of PacBio as a long-read platform has provided new insights, yet HiFi whole-genome sequencing (WGS) cost remains frequently prohibitive. We introduce a targeted sequencing and analysis framework, Twist Alliance Dark Genes Panel (TADGP), designed to offer phased variants across 389 medically important yet complex autosomal genes. We highlight TADGP accuracy across eleven control samples and compare it to WGS. This demonstrates that TADGP achieves variant calling accuracy comparable to HiFi-WGS data, but at a fraction of the cost. Thus, enabling scalability and broad applicability for studying rare diseases or complementing previously sequenced samples to gain insights into these complex genes. TADGP revealed several candidate variants across all cases and provided insight into

Identifiers

PMID38562723
PMCPMC10984040

What OpenQuestion holds

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LicenceCC BY-ND
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.