Top 10 Biorxiv Papers Today in Genetics


2.011 Mikeys
#1. Association analysis of loci implied in'buffering' epistasis
Andres Legarra, Antonio Reverter, Zulma Gladis Vitezica, Marina Naval-Sanchez, Karin Meyer, John Henshall, Fernanda Raidan, Yutao LI, Nicholas J Hudson, Laercio R Porto-Neto
The existence of buffering mechanisms is an emerging property of biological networks, and this results in the possible existence of 'buffering' loci, that would allow buildup of robustness through evolution. So far, there are no explicit methods to find loci implied in buffering mechanisms. However, buffering can be seen as interaction with genetic background. Here we develop this idea into a tractable model for quantitative genetics, in which the buffering effect of one locus with many other loci is condensed into a single (statistical) effect, multiplicative on the total (statistical) additive genetic effect. This allows easier interpretation of the results, and it also simplifies the problem of detecting epistasis from quadratic to linear in the number of loci. Armed with this formulation, we construct a linear model for genome-wide association studies that estimates, and declares significance, of multiplicative epistatic effects at single loci. The model has the form of a variance components, norm reaction model and likelihood...
more | pdf
Figures
None.
Tweets
biorxivpreprint: Association analysis of loci implied in'buffering' epistasis https://t.co/KrtsFSOSo0 #bioRxiv
biorxiv_genetic: Association analysis of loci implied in'buffering' epistasis https://t.co/Enqi6sm7o6 #biorxiv_genetic
evogen_p: RT @biorxiv_genetic: Association analysis of loci implied in'buffering' epistasis https://t.co/Enqi6sm7o6 #biorxiv_genetic
Github
None.
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 10
Total Words: 0
Unqiue Words: 0

2.0 Mikeys
#2. Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions
Solveig K Sieberts, Thanneer Malai Perumal, Minerva M Carrasquillo, Mariet Allen, Joseph S Reddy, Gabriel E Hoffman, Kristen K Dang, John Calley, Phillip J Ebert, James Eddy, Xue Wang, Anna K Greenwood, Sara Mostafavi, the AMP-AD Consortium, the CommonMind Consortium (CMC), Larsson Omberg, Mette Peters, Benjamin A Logsdon, Philip L De Jager, Nilufer Ertekin-Taner, Lara M Mangravite
The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes), and provide the results as a community resource. We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. In addition, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a common resource for use across the community in research programs. As a proof of principle for their utility, we apply a...
more | pdf
Figures
None.
Tweets
biorxivpreprint: Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions https://t.co/kgNVwXvt6O #bioRxiv
biorxiv_genetic: Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions https://t.co/rAOX7CSLhx #biorxiv_genetic
Github

Code base for performing covariate adjustments and differential expression analysis of the RNAseq data from AMP-AD.

Repository: ampad-DiffExp
User: Sage-Bionetworks
Language: R
Stargazers: 0
Subscribers: 5
Forks: 2
Open Issues: 0
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 21
Total Words: 8363
Unqiue Words: 2950

1.999 Mikeys
#3. Identification of pathogenic variant enriched regions across genes and gene families
Eduardo Pérez-Palma, Patrick May, Sumaiya Iqbal, Lisa-Marie Niestroj, Juanjiangmeng Du, Henrike Heyne, Jessica Castrillon, Anne O'Donnell-Luria, Peter Nürnberg, Aarno Palotie, Mark Daly, Dennis Lal
Missense variant interpretation is challenging. Essential regions for protein function are conserved among gene family members, and genetic variants within these regions are potentially more likely to confer risk to disease. Here, we generated 2,871 gene family protein sequence alignments involving 9,990 genes and performed missense variant burden analyses to identify novel essential protein regions. We mapped 2,219,811 variants from the general population into these alignments and compared their distribution with 65,034 missense variants from patients. With this gene family approach, we identified 398 regions enriched for patient variants spanning 33,887 amino acids in 1,058 genes. As a comparison, testing the same genes individually we identified less patient variant enriched regions involving only 2,167 amino acids and 180 genes. Next, we selected de novo variants from 6,753 patients with neurodevelopmental disorders and 1,911 unaffected siblings and observed a 5.56-fold enrichment of patient variants in our identified regions...
more | pdf
Figures
Tweets
biorxivpreprint: Identification of pathogenic variant enriched regions across genes and gene families https://t.co/LWD4bZYaOT #bioRxiv
biorxiv_genetic: Identification of pathogenic variant enriched regions across genes and gene families https://t.co/E7UcqOoObA #biorxiv_genetic
Github

Additional files for the missense burden viewer

Repository: per
User: dlal-group
Language: Perl
Stargazers: 0
Subscribers: 0
Forks: 0
Open Issues: 0
Youtube
None.
Other stats
Sample Sizes : [29222, 1161, 5, 4, 4, 3, 2, 185]
Authors: 12
Total Words: 8134
Unqiue Words: 2436

1.998 Mikeys
#4. Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
Ying Hu, Mohini Ranganathan, Chang Shu, Xiaoyu Liang, Suhas Ganesh, Chunhua Yan, Xinyu Zhang, Bradley E Aouizerat, John H Krystal, Deepak C D'Souza, Ke Xu
Delta 9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, is also known to modulate immune response in peripheral cells. The mechanisms of THC's effects on gene expression in human immune cells remains poorly understood. Combining a within-subject design with single cell transcriptome mapping, we report that administration of THC acutely alters gene expression in 15,973 human blood immune cells. Controlled for high inter-individual transcriptomic variability, we identified 294 transcriptome-wide significant genes among eight cell types including 69 common genes and 225 cell-type specific genes affected by acute THC administration, including those genes involving not only in immune response, cytokine production, but signal transduction, and cell proliferation and apoptosis. We revealed distinct transcriptomic sub-clusters affected by THC in major immune cell types where THC perturbed cell type-specific intracellular gene expression correlations. Gene set enrichment analysis further supports the...
more | pdf
Figures
Tweets
Github
None.
Youtube
None.
Other stats
Sample Sizes : [15973, 2, 2]
Authors: 11
Total Words: 10343
Unqiue Words: 3661

1.998 Mikeys
#5. High-Throughput Single-Molecule R-loop Footprinting Reveals Principles of R-loop Formation
Maika Malig, Stella R Hartono, Jenna M Giafaglione, Lionel A Sanz, Frederic Chedin
R-loops are a prevalent class of non-B DNA structures that form during transcription upon reannealing of the nascent RNA to the template DNA strand. R-loops have been profiled using the S9.6 antibody to immunoprecipitate DNA:RNA hybrids. S9.6-based DNA:RNA immunoprecipitation (DRIP) techniques revealed that R-loops form dynamically over conserved genic hotspots. We developed an orthogonal profiling methodology that queries R-loops via the presence of long stretches of single-stranded DNA on the looped-out strand. Non-denaturing sodium bisulfite treatment catalyzes the conversion of unpaired cytosines to uracils, creating permanent genetic tags for the position of an R-loop. Long read, single-molecule PacBio sequencing allows the identification of R-loop 'footprints' at near nucleotide resolution in a strand-specific manner on single DNA molecules and at ultra-deep coverage. Single-molecule R-loop footprinting (SMRF-seq) revealed a strong agreement between S9.6- and bisulfite-based R-loop mapping and confirmed that R-loops form...
more | pdf
Figures
None.
Tweets
biorxivpreprint: High-Throughput Single-Molecule R-loop Footprinting Reveals Principles of R-loop Formation https://t.co/3CaPJucrKG #bioRxiv
biorxiv_genetic: High-Throughput Single-Molecule R-loop Footprinting Reveals Principles of R-loop Formation https://t.co/dSKF02N7IJ #biorxiv_genetic
sbotlite: RT @biorxivpreprint: High-Throughput Single-Molecule R-loop Footprinting Reveals Principles of R-loop Formation https://t.co/3CaPJucrKG #b…
Github
None.
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 5
Total Words: 0
Unqiue Words: 0

1.997 Mikeys
#6. Sir2 is essential for intergenerational effects of parental diet on offspring metabolism in Drosophila
Ryoya Hayashi, Satomi Takeo, Toshiro Aigaki
Recent studies have revealed that parental diet can affect offspring metabolism and longevity in Drosophila . However, the underlying mechanisms are still unknown. Here we demonstrate that Sir2 encoding an NAD+-dependent histone deacetylase is required for the intergenerational effects of low nutrition diet (1:5 dilution of standard diet). We observed an increased amount of triacylglyceride (TAG) in the offspring when fathers were maintained on a low nutrition diet for 2 days. The offspring had increased levels of metabolites of glycolysis and TCA cycle, the primary energy producing pathways. We found that Sir2 mutant fathers showed no intergenerational effects. RNAi-mediated knockdown of Sir2 in the fat body was sufficient to mimic the Sir2 mutant phenotype, and the phenotype was rescued by transgenic expression of wild-type Sir2 in the fat body. Interestingly, even fathers had no experience of low nutrition diet, overexpression of Sir2 in their fat bodies induced a high level of TAG in the offspring. These findings indicated...
more | pdf
Figures
Tweets
biorxivpreprint: Sir2 is essential for intergenerational effects of parental diet on offspring metabolism in Drosophila https://t.co/3G4h8eESxe #bioRxiv
biorxiv_genetic: Sir2 is essential for intergenerational effects of parental diet on offspring metabolism in Drosophila https://t.co/vSrtm29rvP #biorxiv_genetic
Github
None.
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 3
Total Words: 5136
Unqiue Words: 1507

1.997 Mikeys
#7. Do available protein 3D structures reflect human genetic and functional diversity?
Gregory Sliwoski, Neel Patel, R. Michael Sivley, Charles R. Sanders, Jens Meiler, William S. Bush, John Anthony Capra
Genomic databases are substantially biased towards European ancestry populations, and this bias contributes to health disparities. Here, we quantify how well 66,971 experimentally characterized human protein 3D structures represent the diversity of protein sequences observed across the 1000 Genomes Project. More than 85% of available structures do not match a sequence observed in at least one individual, and on average structures match the sequence of 74% of individuals. Nearly 23% of human structures do not match any observed sequences; however, after masking engineered/known mutations, this decreases to ~4%. African ancestry sequences are modestly, but significantly, less likely to be represented by structures (73.5% vs. 74.0%). These differences are mainly driven by the greater genetic diversity of African populations. We identify thousands of variants unrepresented in available structures that influence protein structure and function. Thus, the use of a single structure as representative of "the wild type" protein will often...
more | pdf
Figures
Tweets
biorxivpreprint: Do available protein 3D structures reflect human genetic and functional diversity? https://t.co/dVjrF6Omiu #bioRxiv
biorxiv_genetic: Do available protein 3D structures reflect human genetic and functional diversity? https://t.co/wmzbkl8jGV #biorxiv_genetic
Github
None.
Youtube
None.
Other stats
Sample Sizes : [503, 503]
Authors: 7
Total Words: 17930
Unqiue Words: 6262

1.997 Mikeys
#8. Retrospective Association Analysis of Longitudinal Binary Traits Identifies Important Loci and Pathways in Cocaine Use
Weimiao Wu, Zhong Wang, Ke Xu, Xinyu Zhang, Amei Amei, Joel Gelernter, Hongyu Zhao, Amy C. Justice, Zuoheng Wang
Longitudinal phenotypes have been increasingly available in genome-wide association studies (GWAS) and electronic health record-based studies for identification of genetic variants that influence complex traits over time. For longitudinal binary data, there remain significant challenges in gene mapping, including misspecification of the model for the phenotype distribution due to ascertainment. Here, we propose L-BRAT, a retrospective, generalized estimating equations-based method for genetic association analysis of longitudinal binary outcomes. We also develop RGMMAT, a retrospective, generalized linear mixed model-based association test. Both tests are retrospective score approaches in which genotypes are treated as random conditional on phenotype and covariates. They allow both static and time-varying covariates to be included in the analysis. Through simulations, we illustrated that retrospective association tests are robust to ascertainment and other types of phenotype model misspecification, and gain power over previous...
more | pdf
Figures
Tweets
Github
None.
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 9
Total Words: 10424
Unqiue Words: 2475

1.997 Mikeys
#9. SYCP2 translocation-mediated dysregulation and frameshift variants cause human male infertility
Samantha LP Schilit, Shreya Menon, Corinna Friedrich, Tammy Kammin, Ellen Wilch, Carrie Hanscom, Sizun Jiang, Sabine Kliesch, Michael E Talkowski, Frank Tüttelmann, Amy J MacQueen, Cynthia C Morton
Infertility is one of the most common disorders for men of reproductive age. To identify novel genetic etiologies, we studied a male with severe oligozoospermia and 46,XY,t(20;22)(q13.3;q11.2). We identified exclusive overexpression of SYCP2 from the der(20) allele that is hypothesized to result from enhancer adoption. Modeling the dysregulation in budding yeast resulted in disruption of the synaptonemal complex, a common cause of defective spermatogenesis in mammals. Exome sequencing of infertile males revealed three novel heterozygous SYCP2 frameshift variants in additional subjects with cryptozoospermia and azoospermia. This study provides the first evidence of SYCP2 -mediated male infertility in humans.
more | pdf
Figures
Tweets
Github
None.
Youtube
None.
Other stats
Sample Sizes : [3, 6]
Authors: 12
Total Words: 12582
Unqiue Words: 3745

1.996 Mikeys
#10. Centromere-proximal meiotic crossovers in Drosophila melanogaster are suppressed by both highly-repetitive heterochromatin and the centromere effect
Michaelyn Hartmann, James Umbanhowar, Jeff Sekelsky
Crossovers are essential in meiosis of most organisms to ensure the proper segregation of chromosomes. The lack or improper placement of crossovers can result in nondisjunction and aneuploidy in progeny. Crossovers near the centromere can cause nondisjunction; centromere-proximal crossovers are suppressed by what is termed the centromere effect, but the mechanism is unknown. Here, we investigate contributions to centromere-proximal crossover suppression in Drosophila melanogaster . We mapped a large number of centromere-proximal crossovers and find that crossovers are essentially absent from the highly-repetitive (HR)-heterochromatin surrounding the centromere but occur at a low frequency within the less-repetitive (LR)-heterochromatic region and adjacent euchromatin. Previous research suggested that flies that lack the Bloom syndrome helicase (Blm) lose meiotic of crossover patterning, including the centromere effect. Mapping of centromere-proximal crossovers in Blm mutants reveals that the suppression within the...
more | pdf
Figures
None.
Tweets
Github
None.
Youtube
None.
Other stats
Sample Sizes : None.
Authors: 3
Total Words: 0
Unqiue Words: 0

About

Assert is a website where the best academic papers on arXiv (computer science, math, physics), bioRxiv (biology), BITSS (reproducibility), EarthArXiv (earth science), engrXiv (engineering), LawArXiv (law), PsyArXiv (psychology), SocArXiv (social science), and SportRxiv (sport research) bubble to the top each day.

Papers are scored (in real-time) based on how verifiable they are (as determined by their Github repos) and how interesting they are (based on Twitter).

To see top papers, follow us on twitter @assertpub_ (arXiv), @assert_pub (bioRxiv), and @assertpub_dev (everything else).

To see beautiful figures extracted from papers, follow us on Instagram.

Tracking 128,326 papers.

Search
Sort results based on if they are interesting or reproducible.
Interesting
Reproducible
Feedback
Online
Stats
Tracking 128,326 papers.