HAT: De novo variant calling for highly accurate short-read and long-read sequencing data

MOTIVATION: de novo variants (DNVs) are variants that are present in offspring but not in their parents. DNVs are both important for examining mutation rates as well as in the identification of disease-related variation. While efforts have been made to call DNVs, calling of DNVs is still challenging from parent-child sequenced trio data. We developed Hare And Tortoise (HAT) as an automated DNV detection workflow for highly accurate short-read and long-read sequencing data. Reliable detection of DNVs is important for human genomics and HAT addresses this need. RESULTS: HAT is a computational workflow that begins with aligned read data (i.e. CRAM or BAM) from a parent-child sequenced trio and outputs DNVs. HAT detects high-quality DNVs from Illumina short-read whole-exome sequencing, Illumina short-read whole-genome sequencing, and highly accurate PacBio HiFi long-read whole-genome sequencing data. The quality of these DNVs is high based on a series of quality metrics including number of DNVs per individual, percent of DNVs at CpG sites, and percent of DNVs phased to the paternal chromosome of origin. AVAILABILITY AND IMPLEMENTATION: https://github.com/TNTurnerLab/HAT

A Note from the Tapestries Editors

Introduction to volume 11 of Macalester College\u27s journal Tapestries: Interwoven voices of local and global identities

Coding and noncoding variants in EBF3 are involved in HADDS and simplex autism

BACKGROUND: Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. RESULTS: We adapted the fitDNM statistical model to work in noncoding regions and tested enhancers for excess of DNVs in families with autism. We found only one enhancer (hs737) with nominal significance in the discovery (p = 0.0172), replication (p = 2.5 × 10 CONCLUSIONS: In this study, we identify DNVs in the hs737 enhancer in individuals with autism. Through multiple approaches, we find hs737 targets the gene EBF3 that is genome-wide significant in NDDs. By assessment of noncoding variation and the genes they affect, we are beginning to understand their impact on gene regulatory networks in NDDs

Primordial Magnetic Fields from Dark Energy

Evidences indicate that the dark energy constitutes about two thirds of the critical density of the universe. If the dark energy is an evolving pseudo scalar field that couples to electromagnetism, a cosmic magnetic seed field can be produced via spinoidal instability during the formation of large-scale structures.Comment: Discussion on back reaction is added to match the published versio

Twenty-three novel HLA-B alleles identified during intermediate-resolution testing

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65805/1/j.1399-0039.2006.00661.x.pd

ACES: Analysis of Conservation with an Extensive list of Species

MOTIVATION: An abundance of new reference genomes is becoming available through large-scale sequencing efforts. While the reference FASTA for each genome is available, there is currently no automated mechanism to query a specific sequence across all new reference genomes. RESULTS: We developed ACES (Analysis of Conservation with an Extensive list of Species) as a computational workflow to query specific sequences of interest (e.g., enhancers, promoters, exons) against reference genomes with an available reference FASTA. This automated workflow generates BLAST hits against each of the reference genomes, a multiple sequence alignment file, a graphical fragment assembly file, and a phylogenetic tree file. These data files can then be used by the researcher in several ways to provide key insights into conservation of the query sequence. AVAILABILITY: ACES is available at https://github.com/TNTurnerLab/ACES. SUPPLEMENTARY INFORMATION: Supplementary Figure 1 is available online in Bioinformatics

Extreme Premature Small for Gestational Age Infants Have Appropriate Catch-up Growth at Term Equivalence Compared with Extreme Premature Appropriate for Gestational Age Infants

Recent studies have shown that small for gestational age (SGA) term infants undergo catch-up growth during infancy but there is limited studies on early growth outcomes of extreme premature SGA infants. The aim of this study was to compare factors associated during birth in extremely premature infants less than 28 weeks’ gestation who were born SGA (<10th percentile for gestational age) with those who were born appropriate-for-gestational age (AGA) (10th-89th percentile) and to determine whether there was catch-up growth at term equivalence. One hundred fifty-three extreme premature infants (89 males) born below 28 weeks’ gestation were prospectively recruited. All infants had auxological measurements undertaken and prospective data on pregnancy, maternal factors, perinatal and postnatal data obtained. SGA infants at birth had significantly higher Clinical Risk Index for Babies scores and mortality, lower birth weight, smaller head circumference, smaller mid arm circumference and shorter leg length at time of birth compared with AGA infants. However, at term equivalence, weight and leg length of were not significant between AGA and SGA infants born at extreme prematurity. Our study shows that extreme premature SGA infants have appropriate catch-up growth by the time they reach term equivalence suggesting that postnatal nutrition and care are important determinants of catch-up growth in SGA infants