A proteogenomic atlas of the human neural retina.

The human neural retina is a complex tissue with abundant alternative splicing and more than 10% of genetic variants linked to inherited retinal diseases (IRDs) alter splicing. Traditional short-read RNA-sequencing methods have been used for understanding retina-specific splicing but have limitations in detailing transcript isoforms. To address this, we generated a proteogenomic atlas that combines PacBio long-read RNA-sequencing data with mass spectrometry and whole genome sequencing data of three healthy human neural retina samples.

Multi-omic profiling of pathogen-stimulated primary immune cells.

We performed long-read transcriptome and proteome profiling of pathogen-stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors to discover new transcript and protein isoforms expressed during immune responses to diverse pathogens. Long-read transcriptome profiling reveals novel sequences and isoform switching induced upon pathogen stimulation, including transcripts that are difficult to detect using traditional short-read sequencing. Widespread loss of intron retention occurs as a common result of all pathogen stimulations.

Benchmarking deep learning splice prediction tools using functional splice assays.

Hereditary disorders are frequently caused by genetic variants that affect pre-messenger RNA splicing. Though genetic variants in the canonical splice motifs are almost always disrupting splicing, the pathogenicity of variants in the noncanonical splice sites (NCSS) and deep intronic (DI) regions are difficult to predict. Multiple splice prediction tools have been developed for this purpose, with the latest tools employing deep learning algorithms.