Biology subjects

Ortigas-Vasquez, A.

Publications and source records attributed to Ortigas-Vasquez, A..

4 recordsLinked to original sources

bioRxiv2026

Measuring satellite arrays of the human Y chromosome from sequencing reads

Human Y chromosome satellites vary widely but remain difficult to measure in large cohorts. In response, we developed Yruler, which uses pangenome assemblies to measure satellite lengths, composition and Y dosage from sequencing reads without alignment. Analyses reveal centromere-length differences between related lineages, extend observations of short non-centromeric arrays across a lineage, and show unequal component variability and composition changes with heterochromatin length within lineages. Yruler brings satellite variation into population-scale phenotype studies.

genomics↗

bioRxiv2025

High-Fidelity Long-Read Sequencing of an Avian Herpesvirus Reveals Extensive Intrapopulation Diversity in Tandem Repeat Regions

Comparative genomic studies of Mareks disease virus (MDV) have suggested that attenuated and virulent strains share >98% sequence identity. However, these estimates fail to account for variation in regions of the MDV genome harboring tandem repeats. To resolve these loci and enable assessments of intrapopulation diversity, we used a PacBio Sequel II platform to sequence MDV strains CVI988/Rispens (attenuated), HPRS-B14 (virulent), Md5 (very virulent) and 675A (very virulent plus). This approach enabled us to identify patterns of variation in tandem repeat regions that are consistent with known phenotypic differences across these strains. We also found CVI988/Rispens variants showing a 4.3-kb deletion in the Unique Short (US) region, resulting in the loss of five genes. These findings support a potential link between MDV tandem repeats and phenotypic traits like virulence and attenuation, and demonstrate that DNA viruses can harbor high levels of intrapopulation diversity in tandem repeat regions.

microbiology↗

bioRxiv2023

Deep Whole-Genome Resequencing of Marek's Disease Virus Strains Reveals Intrastrain Variation

Current strategies to understand the molecular basis of Mareks disease virus (MDV) virulence primarily consist of cataloguing divergent nucleotides between strains with different phenotypes. However, each MDV strain is typically represented by a single consensus genome despite the confirmed existence of mixed viral populations. To assess the reliability of single-consensus interstrain genomic comparisons, we obtained two additional consensus genomes of vaccine strain CVI988 (Rispens) and two additional consensus genomes of the very virulent strain Md5 by sequencing viral stocks and cultured field isolates. In conjunction with the published genomes of CVI988 and Md5, this allowed us to perform 3-way comparisons between consensus genomes of the same strain. We found that consensus genomes of CVI988 can vary in as many as 236 positions involving 13 open reading frames (ORFs). In contrast, we found that Md5 genomes varied only in 11 positions involving a single ORF. Phylogenomic analyses showed all three Md5 consensus genomes clustered closely together, while also showing that CVI988GenBank.BAC diverged from CVI988Pirbright.lab and CVI988USDA.PA.field. Comparison of CVI988 consensus genomes revealed 19 SNPs in the unique regions of CVI988GenBank.BAC that were not present in either CVI988Pirbright.lab or CVI988USDA.PA.field. Finally, we evaluated the genomic heterogeneity of CVI988 and Md5 populations by identifying positions with >2% read support for alternative alleles in two ultra-deeply sequenced samples. We were able to confirm that both populations of CVI988 and Md5 were mixed, exhibiting a total of 29 and 27 high-confidence minor variant positions, respectively. We did not find any evidence of minor variants in the positions corresponding to the 19 SNPs in the unique regions of CVI988GenBank.BAC. Taken together, our findings confirm that consensus genomes of the same strain of MDV can vary and suggest that multiple consensus genomes per strain are needed in order to maximize the accuracy of interstrain genomic comparisons.

microbiology↗

bioRxiv2020

Human papillomavirus type 16 sub-lineages and integration in cancer

Our lab has been intrigued by the fact that viral genomes often take on the role of mobile elements to perpetuate their existence in a complex organisms genome. Multiple DNA viruses such as Epstein-Barr virus, hepatitis B virus, and human papillomavirus (HPV) can invade their host genome, as "genomic parasites". We have been investigating HPV type 16 (HPV16), which is a prominent human tumour virus. In our recent in vitro work using 3D organoids, a common variant of HPV16s coding region elicited early integration into the host genome compared to the HPV16 prototype sequence. Next-generation sequencing (NGS) data confirmed a transcriptomic profile of increased proliferation and chromosomal instability--both hallmarks of cancer. Epidemiologically, this variant is associated with a high cervical cancer incidence. To take inquiries a step further, we investigated variant-specific integration across HPV16-related cancers using NGS data from population-derived clinical samples in The Cancer Genome Atlas (TCGA)-curated database. Data were analyzed for HPV16 positivity, sub-lineage, and viral-host integration using a bioinformatic pipeline of open-source tools, including HPVDetector. Here, we report the analysis of 120 cervical cancer cases comprising HPV16 positive and negative samples as well as their different sub-lineage and integration status. The integration signature between variant and prototype did not differ quantitatively but qualitatively: that of the variant being related to hypoxia/energetics (Warburg effect) and that of the prototype being much more varied to include host immune abrogation and cancer pathways activation. We conclude by discussing challenges and future directions for expanding these analyses.

cancer biology↗