Integrative transcriptomic and metabolomic analysis conjures critical pathways that modulate protein aggregation in a TDP-43 Yeast model of Amyotrophic Lateral Sclerosis

Transcriptomic analysis of yeast model of ALS expressing TDP43 wild type or TDP43 mutant (Q331K) has been carried out. The experiments have been carried out in 3 biological replicates. Fluorescence microscopy showed that both wild type and mutant TDP43 shows amyloid foci which is more intense in mutant. The significant differential genes were further binned into pathways. An integrated Transcriptomic and metabolomic analysis of the yeast model of ALS has been performed using the significant differential genes and metabolites. The results show considerable concurrence in pathways. Further, metabolic addition experiments and gene knock out experiments has been carried out to delineate the role of deregulated pathway in amyloid formation with implications for disease. The results show potential biomarkers and therapeutic targets and therapeutic agents in ALS.