Biology subjects

Almarri, M. A.

Publications and source records attributed to Almarri, M. A..

6 recordsLinked to original sources

bioRxiv2026

Benchmarking Nanopore Sequencing for Autosomal and Y-STR profiling on R10.4.1 Flowcells across Basecalling Models

Short tandem repeat (STR) profiling is the cornerstone of forensic DNA analysis, traditionally performed via capillary electrophoresis. Recently, next generation sequencing has gained prominence due to its increased discriminatory power and enhanced performance with degraded samples. Nanopore sequencing offers a portable and cost-effective alternative, however historically high error rates have precluded its forensic adoption. Here, we evaluate R10.4.1 flow cell chemistry and multiple basecalling tiers (HAC, SUP, HYP) across several iterations (v4.2, v5.0, v5.2, v6.0) to assess their impact on genotyping accuracy. Analyzing 45 STR loci (22 autosomal and 23 Y-STRs) across single-source controls, we introduce a parallelized, user-friendly pipeline designed to transform raw POD5 files into STR profiles. Our results demonstrate a progressive improvement in genotyping accuracy with each basecalling iteration, with the latest models achieving 99.0% autosomal and 100% Y-STR concordance. Furthermore, we find that filtering on raw-read quality scores significantly improves genotyping by reducing background noise and generating cleaner profiles. Notably, the HYPv5.0 Q20 filter drove an average 53.2% reduction in misaligned reads across all loci in comparison to earlier basecalling models. Our study demonstrates that continual bioinformatic improvements in basecalling models, coupled with R10.4.1 chemistry, can provide accurate STR profiles in single-source samples, warranting larger validation studies with more diverse samples to further evaluate performance.

genetics↗

bioRxiv2024

Himalayan whole-genome sequences provide insight into population formation and adaptation

High-altitude environments pose substantial challenges for human survival and reproduction, attracting considerable attention to the demographic and adaptive histories of high-altitude populations. Previous work focused mainly on Tibetans, establishing their genetic relatedness to East Asians and their genetic adaptation to high altitude, especially at EPAS1. Here, we present 87 new whole-genome sequences from 16 Himalayan populations and the insight they provide into the genomic history of the region. We show that population structure in the Himalayas began to emerge as early as 10,000 years ago, predating archaeological evidence of permanent habitation above 2,500 meters by approximately 6,000 years. The high prevalence of the introgressed adaptive EPAS1 haplotype in all high-altitude populations today supports a shared genetic origin and its importance for survival in this region. We also identify additional selection signals in genes associated with hypoxia, physical activity, immunity and metabolism which could have facilitated adaptation to the harsh environment. Over time, increasing genetic structure led to the diverse and strongly differentiated ethnic groups observed today, most of which maintained small population sizes throughout their history or experienced severe bottlenecks. Between 6,000 and 3,000 years ago, a few uniparental lineages became predominant, likely coinciding with the advent of agriculture, although significant population growth was not observed in the Himalayas except in the Tibetans. In more recent times, we detect bidirectional gene flow between high-altitude and lowland groups, occurring on both sides of the Himalayan range. The timing of this admixture aligns with the rise and expansion of historical regional powers, particularly during the Tibetan Empire and the northern Indian Gupta Empire. In the past few centuries, migrations to the Himalayas seem to have occurred alongside conflicts and population displacements in nearby regions and show some sex bias.

genomics↗

bioRxiv2023

Ancient genomes illuminate Eastern Arabian population history and adaptation against malaria

The harsh climate of Arabia has posed challenges in generating ancient DNA from the region, hindering the direct examination of ancient genomes for understanding the demographic processes that shaped Arabian populations. In this study, we report whole genome sequence data obtained from four Tylos-period individuals from Bahrain. Their genetic ancestry can be modelled as a mixture of sources from ancient Anatolia, Levant and Iran/Caucasus, with variation between individuals suggesting population heterogeneity in Bahrain before the onset of Islam. We identify the G6PD Mediterranean mutation associated with malaria-resistance in three out of four ancient Bahraini samples and estimate that it rose in frequency in Eastern Arabia from 5-6 kya onwards, around the time agriculture appeared in the region. Our study provides the first characterisation of the genetic composition of ancient Arabians, shedding light on the population history of Bahrain and demonstrating the feasibility of aDNA studies in the region.

genomics↗

bioRxiv2020

The Genomic History of the Middle East

The Middle East is an important region to understand human evolution and migrations, but is underrepresented in genetic studies. We generated and analysed 137 high-coverage physically-phased genome sequences from eight Middle Eastern populations using linked-read sequencing. We found no genetic traces of early expansions out-of-Africa in present-day populations, but find Arabians have elevated Basal Eurasian ancestry that dilutes their Neanderthal ancestry. A divergence in population size within the region starts before the Neolithic, when Levantines expanded while Arabians maintained small populations that could have derived ancestry from local epipaleolithic hunter-gatherers. All populations suffered a bottleneck overlapping documented aridification events, while regional migrations increased genetic structure, and may have contributed to the spread of the Semitic languages. We identify new variants that show evidence of selection, some dating from the onset of the desert climate in the region. Our results thus provide detailed insights into the genomic and selective histories of the Middle East.

genomics↗

bioRxiv2019

Population Structure, Stratification and Introgression of Human Structural Variation in the HGDP.

Structural variants contribute substantially to genetic diversity and are important evolutionarily and medically, yet are still understudied. Here, we present a comprehensive analysis of deletions, duplications, insertions, inversions and non-reference unique insertions in the Human Genome Diversity Project (HGDP-CEPH) panel, a high-coverage dataset of 911 samples from 54 diverse worldwide populations. We identify in total 126,018 structural variants (25,588 <100 bp in size), of which 78% are novel. Some reach high frequency and are private to continental groups or even individual populations, including a deletion in the maltase-glucoamylase gene MGAM involved in starch digestion, in the South American Karitiana and a deletion in the Central African Mbuti in SIGLEC5, potentially leading to immune hyperactivity. We discover a dynamic range of copy number expansions and find cases of regionally-restricted runaway duplications, for example, 18 copies near the olfactory receptor OR7D2 in East Asia and in the clinically-relevant HCAR2 in Central Asia. We identify highly-stratified putatively introgressed variants from Neanderthals or Denisovans, some of which, like a deletion within AQR in Papuans, are almost fixed in individual populations. Finally, by de novo assembly of 25 genomes using linked-read sequencing we discover 1631 breakpoint-resolved unique insertions, in aggregate accounting for 1.9 Mb of sequence absent from the GRCh38 reference. These insertions show population structure and some reside in functional regions, illustrating the limitation of a single human reference and the need for high-quality genomes from diverse populations to fully discover and understand human genetic variation.

genomics↗

bioRxiv2019

Insights into human genetic variation and population history from 929 diverse genomes

Genome sequences from diverse human groups are needed to understand the structure of genetic variation in our species and the history of, and relationships between, different populations. We present 929 high-coverage genome sequences from 54 diverse human populations, 26 of which are physically phased using linked-read sequencing. Analyses of these genomes reveal an excess of previously undocumented private genetic variation in southern and central Africa and in Oceania and the Americas, but an absence of fixed, private variants between major geographical regions. We also find deep and gradual population separations within Africa, contrasting population size histories between hunter-gatherer and agriculturalist groups in the last 10,000 years, a potentially major population growth episode after the peopling of the Americas, and a contrast between single Neanderthal but multiple Denisovan source populations contributing to present-day human populations. We also demonstrate benefits to the study of population relationships of genome sequences over ascertained array genotypes. These genome sequences are freely available as a resource with no access or analysis restrictions.

genomics↗