🧩📊 Characterizing haplotype-specific regulation in aneuploidy
From March 31 to July 22, 2025, Pablo Angulo Lara had the opportunity to carry out a research secondment at the University of Florida, supervised by Prof. Lauren McIntyre.
Pablo said “this period marked an important milestone in my PhD journey, both scientifically and personally”.
My main objective? During this secondment, I focused on developing a pipeline for allele-specific expression (ASE) analysis in complex karyotypes, integrating transcript expression, DNA copy-number, and DNA methylation data. Building on this framework, I worked on characterizing haplotype-specific regulation in aneuploidy using RPE1 samples, laying the groundwork for robust hypothesis testing in my project.
What I Learned 🎓
Throughout these months, I gained hands-on experience in performing ASE analyses using long-read sequencing data, combining transcriptomic and genomic information. I also deepened my understanding of the biases and sources of error inherent to long-read RNA-seq data, particularly in haplotype-resolved analyses, and explored different statistical models and their limitations when testing allele-specific hypotheses.
Challenges and Takeaways 🧩
The work was not without challenges. One of the main difficulties was the integration of multiple omic layers, genomic, DNA methylation, and transcriptomic data, together with the analysis of haplotype-resolved assemblies characterized by high annotation complexity and inter-haplotype heterogeneity. Tackling these challenges was demanding, but ultimately extremely rewarding.
Impact 🔝
Overall, this secondment allowed me to develop the core methodology of my project, enabling an in-depth characterization of haplotype-specific regulation in aneuploidy and strengthening the analytical foundations of my research.
Beyond the science, spending several months in a research group specialized in the statistical analysis of long-read sequencing data and allele-specific expression was a unique experience. Working in an academic environment with a different culture and perspective, and meeting inspiring researchers along the way, enriched me both professionally and personally.
