Genetic and Genomic Medicine

Design and validation of a clinical whole genome sequencing-based assay for patient screening in a large healthcare system

1. Josiah T. Wagner
2. John T. Welle
3. Isabelle A. Lucas Beckett
4. Kate R. Emery
5. Benjamin A. Cosgrove
6. Krzysztof Olszewski
7. Nick Wagner
8. Tucker C. Bower
9. Li Chi Yuan
10. Eric M. Shull
11. Kathleen Jade
12. Jon Clemens
13. Andrew T. Magis
14. Mary B. Campbell
15. Ora K. Gordon
16. Carlo B. Bifulco
17. Brian D. Piening

Reviewed by PREreview

Adapting clinical chemistry plasma as a source for liquid biopsies

1. Spencer C Ding
2. Jingru Yu
3. Tiepeng Liao
4. Lauren Ahmann
5. Yvette Yao
6. Chandler Ho
7. Linlin Wang
8. Benjamin A Pinsky
9. Wei Gu

• Curated by eLife

  eLife Assessment

  This important work provides a new method to extract cfDNA from residual plasma from heparin separators for molecular testing. The evidence supporting the authors' claims is convincing, although some further metrics should also be evaluated. This finding will be interesting to people working in epigenomics and infectious disease diagnostics.

Reviewed by eLife

Functional Effect Predictions For Ion Channel Missense Variants Using a Protein Language Model

1. Sean Gies
2. Artoghrul Alishbayli
3. Paul H.E. Tiesinga
4. Marijn B. Martens

Reviewed by PREreview

Interactions with polygenic background impact quantitative traits in the UK Biobank

1. Lino A. F. Ferreira
2. Sile Hu
3. Robert W. Davies
4. Simon R. Myers

Reviewed by Arcadia Science

Functional analysis across model systems implicates ribosomal proteins in growth and proliferation defects associated with hypoplastic left heart syndrome

1. Tanja Nielsen
2. Anaïs Kervadec
3. Jeanne L Theis
4. Maria A Missinato
5. James Marchant
6. Michaela Romero
7. Katya Marchetti
8. Aashna Lamba
9. Xin-Xin I Zeng
10. Marie Berenguer
11. Stanley M Walls
12. Analyne Schroeder
13. Katja Birker
14. Greg Duester
15. Paul Grossfeld
16. Timothy J Nelson
17. Timothy M Olson
18. Karen Ocorr
19. Rolf Bodmer
20. Georg Vogler
21. Alexandre R Colas

• Curated by eLife

  eLife Assessment

  This important study applies an innovative multi-model strategy to implicate the ribosomal protein (RP) encoding genes as candidates causing Hypoplastic Left Heart Syndrome. The evidence from the screen in stem cell-derived cardiomyocytes and whole genome sequencing of human patients, followed by functional analyses of RP genes in fly and fish models, is convincing and supports the authors' claims. This work and methodology applied would be of broad interest to medical biologists working on congenital heart diseases.

Reviewed by eLife

Genomic privacy risks in GWAS summary statistics

1. Ao Lan
2. Yudi Pawitan
3. Xia Shen

• Curated by eLife

  eLife Assessment

  This important study provides a theoretical framework for quantifying privacy risk from publicly shared genome-wide association summary statistics. The findings reveal the conditions under which genotype reconstruction may become feasible, challenging long-held assumptions about personal data safety. While the evidence is solid, supported by clear mathematical derivations and simulations, validation on large empirical datasets would further strengthen the claims.

Reviewed by eLife

A titin missense variant drives atrial electrical remodeling and is associated with atrial fibrillation

1. Mahmud Arif Pavel
2. Hanna Chen
3. Michael Hill
4. Arvind Sridhar
5. Miles Barney
6. Jaime DeSantiago
7. Abhinaya Baskaran
8. Asia Owais
9. Shashank Sandu
10. Faisal A Darbar
11. Aylin Ornelas Loredo
12. Bahaa Al-Azzam
13. Brandon Chalazan
14. Jalees Rehman
15. Dawood Darbar

• Curated by eLife

  eLife Assessment

  The study presents important findings regarding the incidence and clinical impact of a mutation in a cardiac muscle protein and its association with the development of atrial fibrillation. The authors provide convincing evidence of electrophysiological disturbances in cells with this mutation and of its association with atrial fibrillation, which would be of interest to cardiologists. Evidence supporting the conclusion that this mutation causes atrial fibrillation would benefit from more rigorous electrophysiologic approaches.

Reviewed by eLife

Monocyte-endothelial interactions as a targetable node in clonal hematopoiesis-mediated cardiovascular disease

1. Alyssa C Parker
2. J Brett Heimlich
3. Joseph C Van Amburg
4. Yash Pershad
5. David A Ong
6. Nicole A Mickels
7. Laventa M Obare
8. Ketan J Hoey
9. Hannah K Giannini
10. Ayesha Ahmad
11. Caitlyn Vlasschaert
12. Tarak N Nandi
13. Ravi K Madduri
14. Samuel S Bailin
15. John R Koethe
16. Celestine N Wanjalla
17. Alexander G Bick

• Curated by eLife

  eLife Assessment

  Clonal hematopoiesis of indeterminate potential (CHIP) is a known risk factor for coronary artery disease, though its precise role in disease progression continues to emerge. This study leverages valuable single-cell RNA data from patients with CHIP mutations and controls to predict key interactions between endothelial cells and monocytes. Using an AI prediction model, the authors identify druggable targets that mediate immune cell interactions in CHIP and provide solid evidence to support their findings.

Reviewed by eLife

Causal associations between human plasma proteins and prostate cancer identified by proteome-wide Mendelian randomization

1. Lin Chen
2. Yanlun Gu
3. Yuke Chen
4. Wei Yu
5. Ying Zhou
6. Zhuona Rong
7. Xiaocong Pang

• Curated by eLife

  eLife Assessment

  This study presents a meta-analysis of two independent genome-wide association studies (GWAS) that investigate the role of plasma proteins as potential biomarkers for enhancing the early detection of prostate cancer (PCa). The results provide useful confirmatory data that support existing evidence currently published. The evidence is incomplete: the study does not provide a comprehensive synthesis of all currently published work, does not explore other clinical outcomes related to prostatic disease, and its findings have not been validated through an external cohort study. These shortcomings notwithstanding, the work may be of interest to researchers studying correlates and predictors of prostate cancer risk.

Reviewed by eLife

Low-dose chemotherapy combined with delayed immunotherapy in the neoadjuvant treatment of non-small cell lung cancer and dynamic monitoring of the drug response in peripheral blood

1. Chaoyang Liang
2. Qi Song
3. Wenhao Zhou
4. Na Li
5. Qi Xiong
6. Chaohu Pan
7. Shaohong Zhao
8. Xiang Yan
9. Xiaoling Zhang
10. Yaping Long
11. Juntang Guo
12. Tao Wang
13. Weiwei Shi
14. Shengjie Sun
15. Bo Yang
16. Zhouhuan Dong
17. Haitao Luo
18. Jie Li
19. Yi Hu
20. Bo Yang

• Curated by eLife

  eLife Assessment

  Liang et al. have conducted a small pilot study investigating the feasibility and tolerability of a regimen of neoadjuvant chemo-immunotherapy for non-small cell lung cancer, with lower cumulative dose of chemotherapy and with the immunotherapy delivered on D8 of each cycle. The clinical data are interesting and novel, and overall the findings of the study are valuable. However, the translational data and analyses are incomplete and do not support key claims in the title.

Reviewed by eLife