Genetics

Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision

1. James A Watson
2. Carolyne M Ndila
3. Sophie Uyoga
4. Alexander W Macharia
5. Gideon Nyutu
6. Mohammed Shebe
7. Caroline Ngetsa
8. Neema Mturi
9. Norbert Peshu
10. Benjamin Tsofa
11. Kirk Rockett
12. Stije Leopold
13. Hugh Kingston
14. Elizabeth C George
15. Kathryn Maitland
16. Nicholas PJ Day
17. Arjen Dondorp
18. Philip Bejon
19. Thomas N Williams
20. Chris C Holmes
21. Nicholas J White

• Curated by eLife

  Evaluation Summary:

  The fundamental premise of genome wide association studies for severe malaria is to take a population with confirmed severe malaria and compare with a control group who do not have severe malaria. This paper presents a novel and valuable method for improving power for severe malaria genetic association studies. The method would also be useful for studies of other disease where there is a clinical definition that sometimes includes people who do not truly have the disease.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Genetic Variant in 3’ Untranslated Region of the Mouse Pycard Gene Regulates Inflammasome Activity

1. Brian Ritchey
2. Qimin Hai
3. Juying Han
4. John Barnard
5. Jonathan D. Smith

• Curated by eLife

  Evaluation Summary:

  Genetic differences in outbred species such as humans and differences in the epigenomic structure form the basis of the large variability in the immune response. This work demonstrates that a single nucleotide change in the gene encoding for the universal inflammasome adaptor protein ASC regulates mRNA stability of Pycard and thereby inflammasome function. A particular strength of the work is that the authors managed to show, using genetic alterations, that a single SNP in the Pycard gene sequence (rs33183533) between AKR and DBA/2 mice causes variation in inflammasome activity. Given the relevance of inflammasome for various human pathologies, this work is important for a broad readership.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Missense variants in human ACE2 strongly affect binding to SARS-CoV-2 Spike providing a mechanism for ACE2 mediated genetic risk in Covid-19: A case study in affinity predictions of interface variants

1. Stuart A. MacGowan
2. Michael I. Barton
3. Mikhail Kutuzov
4. Omer Dushek
5. P. Anton van der Merwe
6. Geoffrey J. Barton

Reviewed by ScreenIT

The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions

1. Braulio Bonilla
2. Alexander J Brown
3. Sarah R Hengel
4. Kyle S Rapchak
5. Debra Mitchell
6. Catherine A Pressimone
7. Adeola A Fagunloye
8. Thong T Luong
9. Reagan A Russell
10. Rudri K Vyas
11. Tony M Mertz
12. Hani S Zaher
13. Nima Mosammaparast
14. Ewa P Malc
15. Piotr A Mieczkowski
16. Steven A Roberts
17. Kara A Bernstein

• Curated by eLife

  Evaluation Summary:

  This paper is of potential interest to an audience of DNA repair and cancer biologists because it seeks to refine the mechanism by which cells respond to DNA damage. By combining a number of genetic experiments based on cell survival of different mutant combinations and mutation analysis, their results support the view that Shu is critical for 3meC damage tolerance in yeast. Notably, expression of human ALKBH2, responsible for the repair of 3meC rescues the MMS-sensitivity of Shu mutants but not that of homologous recombination mutants. The study supports the existence of a new pathway for the removal of an important DNA lesion that seems essential in yeast, but likely contributes in other organisms, and helps clarify the distinctive role of homologous recombination in DSB repair and post-replicative repair. A few additional experiments are suggested to strengthen the mechanistic conclusions and better support the central model.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Genetic variants in TMPRSS2 and Structure of SARS-CoV-2 spike glycoprotein and TMPRSS2 complex

1. Ravikanth Vishnubhotla
2. Naveen Vankadari
3. Vijayasarathy Ketavarapu
4. Ramars Amanchy
5. Steffie Avanthi
6. Govardhan Bale
7. Duvvur Nageshwar Reddy
8. Mitnala Sasikala

Reviewed by ScreenIT

Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics

1. Ersin Akinci
2. Minsun Cha
3. Lin Lin
4. Grace Yeo
5. Marisa C. Hamilton
6. Callie J. Donahue
7. Heysol C. Bermudez-Cabrera
8. Larissa C. Zanetti
9. Maggie Chen
10. Sammy A. Barkal
11. Benyapa Khowpinitchai
12. Nam Chu
13. Minja Velimirovic
14. Rikita Jodhani
15. James D. Fife
16. Miha Sovrovic
17. Philip A. Cole
18. Robert A. Davey
19. Christopher A. Cassa
20. Richard I. Sherwood

Reviewed by Rapid Reviews Infectious Diseases, ScreenIT

Similarity between mutation spectra in hypermutated genomes of rubella virus and in SARS-CoV-2 genomes accumulated during the COVID-19 pandemic

1. Leszek J. Klimczak
2. Thomas A. Randall
3. Natalie Saini
4. Jian-Liang Li
5. Dmitry A. Gordenin

Reviewed by ScreenIT

Structural Variants in SARS-CoV-2 Occur at Template-Switching Hotspots

1. Brianna Chrisman
2. Kelley Paskov
3. Nate Stockham
4. Kevin Tabatabaei
5. Jae-Yoon Jung
6. Peter Washington
7. Maya Varma
8. Min Woo Sun
9. Sepideh Maleki
10. Dennis P. Wall

Reviewed by ScreenIT

Extensive Genetic Diversity and Host Range of Rodent-borne Coronaviruses

1. Wen Wang
2. Xian-Dan Lin
3. Hai-Lin Zhang
4. Miao-Ruo Wang
5. Xiao-Qing Guan
6. Edward C. Holmes
7. Yong-Zhen Zhang

Reviewed by ScreenIT

Paired SARS-CoV-2 Spike Protein Mutations Observed During Ongoing SARS-CoV-2 Viral Transfer from Humans to Minks and Back to Humans

1. Scott Burkholz
2. Suman Pokhrel
3. Benjamin R. Kraemer
4. Daria Mochly-Rosen
5. Richard T. Carback
6. Tom Hodge
7. Paul Harris
8. Serban Ciotlos
9. Lu Wang
10. CV Herst
11. Reid Rubsamen

Reviewed by ScreenIT