Alessandro Paz Hernandez

Alessandro, a junior studying Cellular & Biomolecular Engineering, Biotechnology, and Applied Data Science at Purdue University, developed a pipeline to extract p14/p16 gene expression data from CDKN2A 5’ Single Cell Sequencing data.

Diseases like Alzheimer's, type 2 diabetes, cancer, and coronary artery disease involve a cell identity change that leads to altered cellular functions and senescence. I learned in the first two weeks what I would’ve learned in 2 months. I felt supported enough to accept the person I am and face the person I can become, both personally and professionally. The enthusiastic and curious spirit of all the Broadies I met helped me picture my career more clearly regarding grad school and new research avenues to encounter. Overall, the program showed me exciting avenues ahead, tools to grow as a scientist and an individual, and ways I can support those around me—a life-changing experience. An important genetic site for senescence is the CDKN2A locus. CDKN2A consists of two isoforms, p14ARF & p16INK4a, which differ in exon 1 but share exon 2 and 3. Unlike typical isoforms, these isoforms code for completely distinct amino acid sequences due to a frameshift caused by exon 1. With different sequences, they target different pathways. The p14ARF isoform takes part in the p53 pathway, while p16INK4a takes the Rb pathway. Current sequencing annotations evaluate both isoforms as one gene. We are developing a single-cell sequencing pipeline to estimate how the expression of p14 and p16 varies across different cell types and tissues. This pipeline will quantify p14ARF and p16INK4a expression from published raw 5′ single-cell sequencing data. 5′ sequencing data is less abundant than 3′ sequencing data but is the only direct way to differentiate either gene from exon 1. We will then characterize the co-expression of correlated genes for each specific isoform. This five ′ co-expression profile will then be fed into a machine-learning model to predict p14ARF and p16INK4a expression in 3′ sequencing data. This work will allow us to understand better cell-type specific senescence and the importance of the unique expression of the CDKN2A locus as a factor for aging.

Project: Cell-type specific expression of the CDKN2A isoforms across tissues and disease states analyzing single-cell sequencing

Mentors: Elena Torlai Triglia

PI: Bernstein Lab, Gene Regulation Observatory