SQTL ve HI-C'nin ortak analizi, birden fazla dokuda Sqtller ile hedef genler arasında mekansal yakınlık ortaya çıkarıyor

Gene expression and regulation with or without alternative splicing are crucial for tissues and cells to properly function. They have been studied from three almost independent perspectives at the genome level: 1- Recognition of splicing quantitative trait loci~(sQTLs), 2- Expression quantitative trait loci~(eQTLs) recognition, and 3- Recognition of longer-range physical chromatin interactions between genome segments which model $3$D dynamics of cells and tissues. Even though the associations between eQTLs and longer range chromatin interactions have been previously studied, similar relationship between sQTLs and chromatin interactions has not been previously analyzed. In this case, it is crucial to analyze whether sQTLs control the alternative splicing of their target genes mRNA via physically-interacting genome segments. Even though chromatin interactions are part of the principal processes governing eQTLs functioning, similar analysis is missing from sQTLs perspective. We have jointly analyzed high-throughput chromatin conformation capture~(Hi-C) and sQTL datasets over 8 different human cancer tissues. We have discovered the existence of positive association between the number of genes having sQTLs and chromatin interaction frequency. Such positive association still exists when we also control for eQTLs. Additionally, sQTLs and their target genes generally exist inside identical topologically associating domain~(TAD). Those findings are observed over the whole set of analyzed cancer types and over different functional subsets of sQTL dataset such as survival-related sQTLs. Furthermore, tissue-specific sQTLs are statistically enriched in tissue-specific frequently interacting regions~(FIREs) in 6 out of 8 human cancer tissues~(Chronic Myeloid Leukemia, Colon Adenocarcinoma, Acute Myeloid Leukemia, Lung Adenocarcinoma, Prostate Cancer, Sarcoma). Our sQTL and Hi-C datasets have shown the existence of closer spatial distance between sQTLs and their target genes with possible alternative splicing across a number of different cancer types in human. Such closer spatial distance also exists independent of whether we integrate eQTLs into the analysis. We found that sQTLs regulate the alternative splicing through chromatin interactions.