Balogun, O. | Search bioRxiv

bioRxiv2025

Uncovering Functional Sequence Gaps in Human Reference Genomes using African Pan Genome Contig Sequences

Human reference genomes underpin biomedical discovery but remain incomplete and biased toward European populations, constraining interpretation of genetic variation in underrepresented populations. Here we characterize African Pan Genome (APG) contigs totaling 296.5 Mb to define the sequence and functional landscape of genomic regions absent from current references. Most contigs align to the telomere-to-telomere (T2T-CHM13) genome and across 47 haplotype-resolved Human Pangenome Reference Consortium (HPRC) assemblies, with T2T-CHM13 placements enriched in centromeric and satellite repeats and overlapping 373 genes, including disease-associated loci. Mapping across HPRC assemblies revealed ancestry-associated contig enrichment, particularly in African genomes. Notably, 742 contigs remained unmapped under both stringent and relaxed criteria. These sequences are largely nonrepetitive and exhibit strong functional potential, including predicted protein-coding genes, CpG islands and transcriptional activity. Together, these results demonstrate that functionally relevant, ancestry-enriched genomic sequences remain absent from current references, with important implications for disease variant interpretation and precision medicine.

genomics↗

bioRxiv2024

Soft, 3D printed muscle ultrasound phantom with structurally tunable B-mode echo intensity

OBJECTIVESImaging phantoms for training and validation are vital to improving the performance and adoption of ultrasound imaging modalities in clinical and pre-clinical applications, and the goal of this study was to assess the viability of 3D printed muscle ultrasound phantoms to meet this need. METHODSWe used a soft stereolithography resin to 3D print phantoms that mimicked the fascicle- and perimysium-scale structure of skeletal muscle and compared the long axis B-mode imaging quality and pattern of the phantom to that of healthy, adult Biceps brachii. We used a pulse-echo, time-of-flight method to measure the acoustic impedance of the resin for comparison to skeletal muscle and common soft tissue mimicking materials. We analyzed the echo intensity (EI) of muscle images to establish a physiological range and compared the EI of different phantom designs to assess the ability to control imaging brightness through structural modification. RESULTSA linear, striated hyper-/hypo-echoic B-mode imaging pattern mimicking long axis Biceps brachii muscle images was achieved with two 3D structure paradigms, rod and honeycomb. Acoustic impedance of Elastic 50A resin is higher than skeletal muscle in bulk, but appears suitable for use in a 3D structured phantom. EI measured in the Biceps images were found to vary both within and across images with an overall mean {+/-} SD of 87 {+/-}13 AU. EI measured in honeycomb phantoms (55 {+/-}15 AU) was higher than in rod phantoms (42 {+/-}13 AU), and a latticed honeycomb further increased EI (90 {+/-}11 AU). CONCLUSIONSThis study serves as proof-of-concept for soft, 3D printed phantoms that replicate the characteristic muscle ultrasound imaging pattern with the ability to tune clinically relevant EI values via structural design.

bioengineering↗