static void GenerateGVF(DataRow dataRow)
{
List<string> gvfLines = new List<string>();
gvfLines.Add("##gff-version 3");
gvfLines.Add("##gvf-version 1.04");
gvfLines.Add("##file-version 1.03");
gvfLines.Add(string.Format("##file-date {0}", dataRow.ResultedOn.ToString("yyyy-MM-dd")));
gvfLines.Add("");
gvfLines.Add(string.Format("##individual-id Dbxref={0}:{1};First_name={2};Last_name={3};DOB={4};",
dataRow.MRNSource, dataRow.MRN, dataRow.FirstName, dataRow.LastName, dataRow.ResultedOn.ToString("yyyy-MM-dd")));
gvfLines.Add("##source-method Source=SOLiD;Type=SNV;Dbxref=http://tinyurl.com/AB-Genome-Data;Comment=SNPs were detected across the three genomes via a heuristic approach which considers the number of reads per allele as well as a score which weights the SNP calls based on the error profile of the reads;");
gvfLines.Add("##source-method Source=SOLiD;Type=SNV;Dbxref=http://www.yandell-lab.org;Comment=Variants were converted their from original format to GVF by the Yandell Lab;");
gvfLines.Add("##technology-platform Source=SOLiD;Type=SNV;Dbxref=http://solid.appliedbiosystems.com;Platform_class=short read sequencing;Platform_name=AB SOLiD;Read_type=pair,fragment;Read_length=25;Read_pair_span=600,3500;Average_coverage=26;");
//gvfLines.Add("##phenotype-description Ontology=http://obofoundry.org/wiki/index.php/PATO:Main_Page;Term=female");
gvfLines.Add("##feature-ontology http://sourceforge.net/projects/song/files/SO_Feature_Annotation/sofa_2_4_1/sofa_2_4_1.obo/download");
gvfLines.Add("##genome-build GRCh38");
gvfLines.Add("");
gvfLines.Add("##sequence-region chr1 1 247249719");
gvfLines.Add("##sequence-region chr10 1 135374737");
gvfLines.Add("##sequence-region chr11 1 134452384");
gvfLines.Add("##sequence-region chr14 1 106368585");
gvfLines.Add("##sequence-region chr15 1 100338915");
gvfLines.Add("##sequence-region chr16 1 88827254");
gvfLines.Add("");
foreach (var snp in dataRow.SNPs)
{
gvfLines.Add(string.Format("chr{0}\tSOLiD\tSNV\t{1}\t{2}\t.\t+\t.\tID={3};Reference_seq={4};{5}",
snp.Chromosome, snp.Position, snp.Position, snp.RSID, Lookup.GetSNPReferenceValue(snp.RSID), GetVariant(snp)));
}
File.WriteAllLines(Path.Combine(ConfigurationManager.AppSettings["GVFDirectory"], dataRow.MRN + ".gvf"), gvfLines);
}
static void GenerateGVF(DataRow dataRow)
{
List<string> vcfLines = new List<string>();
vcfLines.Add("##fileformat=VCFv4.0");
vcfLines.Add(string.Format("##fileDate={0}", dataRow.ResultedOn.ToString("yyyyMMdd")));
vcfLines.Add("##reference=GRCh38");
vcfLines.Add("##phasing=partial");
vcfLines.Add(string.Format("##individual-id=<Dbxref={0}:{1},First_name={2},Last_name={3},DOB={4}>",
dataRow.MRNSource, dataRow.MRN, dataRow.FirstName, dataRow.LastName, dataRow.ResultedOn.ToString("yyyy-MM-dd")));
vcfLines.Add("##INFO=<ID=NS,Number=1,Type=Integer,Description=\"Number of Samples With Data\">");
vcfLines.Add("##INFO=<ID=DP,Number=1,Type=Integer,Description=\"Total Depth\">");
vcfLines.Add("##INFO=<ID=AF,Number=.,Type=Float,Description=\"Allele Frequency\">");
vcfLines.Add("##INFO=<ID=AA,Number=1,Type=String,Description=\"Ancestral Allele\">");
vcfLines.Add("##INFO=<ID=DB,Number=0,Type=Flag,Description=\"dbSNP membership, build 129\">");
vcfLines.Add("##INFO=<ID=H2,Number=0,Type=Flag,Description=\"HapMap2 membership\">");
vcfLines.Add("##FILTER=<ID=q10,Description=\"Quality below 10\">");
vcfLines.Add("##FILTER=<ID=s50,Description=\"Less than 50% of samples have data\">");
vcfLines.Add("##FORMAT=<ID=GQ,Number=1,Type=Integer,Description=\"Genotype Quality\">");
vcfLines.Add("##FORMAT=<ID=GT,Number=1,Type=String,Description=\"Genotype\">");
vcfLines.Add("##FORMAT=<ID=DP,Number=1,Type=Integer,Description=\"Read Depth\">");
vcfLines.Add("#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT\tSample1");
foreach (var snp in dataRow.SNPs)
{
string reference = Lookup.GetSNPReferenceValue(snp.RSID);
// For insertions, we need to back up one position and provide the reference at that
// location.
if (snp.RSID == "rs397515963")
{
reference = "G";
snp.Position -= 1;
}
List<string> alleles = GetVariants(snp, reference);
vcfLines.Add(string.Format("{0}\t{1}\t{2}\t{3}\t{4}\t50\tPASS\tNS=1;DP=10;AA={3};DB\tGT:GQ:DP\t{5}:50:10",
snp.Chromosome, snp.Position, snp.RSID, reference, FormatAlternateAlleles(snp.RSID, alleles),
FormatSampleGenotype(snp, alleles, reference)));
}
File.WriteAllLines(Path.Combine(ConfigurationManager.AppSettings["VCFDirectory"], dataRow.MRN + ".vcf"), vcfLines);
}
static void Main(string[] args)
{
// Read in our list of patients and their corresponding randomization variables
var data = File.ReadAllLines(ConfigurationManager.AppSettings["GVFList"]);
foreach (var dataLine in data.Skip(1))
{
var fields = dataLine.Split(Delimiter);
var dataRow = new DataRow()
{
MRN = fields[0],
MRNSource = fields[1],
FirstName = fields[2],
LastName = fields[3],
DOB = DateTime.Parse(fields[4]),
ResultedOn = DateTime.Parse(fields[5]),
Lab = fields[6],
SNPs = new List<SnpResult>()
};
for (int fieldIndex = 7; fieldIndex < 135; fieldIndex += 4)
{
var snp = new SnpResult()
{
RSID = fields[fieldIndex],
Chromosome = fields[fieldIndex + 1],
Position = int.Parse(fields[fieldIndex + 2]),
Genotype = fields[fieldIndex + 3]
};
dataRow.SNPs.Add(snp);
}
GenerateGVF(dataRow);
}
}