Gene_Network_Variant_Dataset_mTOR_TGF_Beta

The mTOR and TGF-Beta pathway genes were selected based on KEGG database (https://www.genome.jp/kegg/). Genomic sequences of the pathway genes were fetched from GRCh37 human genome database based on their genomic coordinates recorded in NCBI database (https://www.ncbi.nlm.nih.gov/projects/genome/guide/human/index.shtml).<br>Reference sequences composed of each gene sequence were used as a template to generate 400 control and 400 patient sequences for each pathway. At the first step, we created two lists of integers for both groups, thatrepresent the positions of polymorphic and pathogenic variants (‘polymorphic positions list’and ‘pathogenic positions list’). Each integer in these lists has been randomly chosen to be within certain consecutive intervals and exclusive to the other list. This interval has been set to 100 and 200 for polymorphic and pathogenic variants, respectively (Any integer within the range 1-100, 100-200, 200-300, and so on, for ‘polymorphic positions list’, and any integer within the range 1-200, 200-400, 400-600, and so on, for ‘pathogenic positions list’). In the second step, the reference base at each position represented in ‘polymorphicpositions list’ was replaced by the variant base in 40% of both control and patient sequences. The alterations in these positions were accepted as non-pathogenic and/or common variants with 0.40 minor allele frequency in both groups. In the next step, reference base at each position represented in ‘pathogenic positions list’was replaced by the variant base in 25% of control sequences and 30% of patient sequences. The alterations in these positions were accepted as disease-associated/pathogenic variants with 0.25 allele frequency in the control group and 0.30 allele frequency in the patient group. In all these steps, we set minor allele frequency (MAF) higher, because, in contrary to single-gene disorders where rare variants (with MAF&lt; 0.01) are causative, complex disorders are the consequences of the combination of the variants with higher allele frequency (MAF&gt; 0.01).All variant sequences are in haploid state.