# If I have data from a full genome sequence, how can I search for a known pathogenic variant of a known gene?

I have a CS background, but am a bioinformatics neophyte

I did a full genome sequence which provided me with ~100GB of files (SNP VCF, Indel VCF, BAM, Indel TBI, SNP TBI, BAM BAI, CNV VCF, CNV TBI, CV VCF, SV TBI, FASTQ R1, and FASTQ R2).

I'd like to search the genome for a pathogenic variant of a known gene. What tools do I need to do this, or where do I start?

• Hi and welcome @ensnare Is only the gene known? or is the specific variant known as well? What format is the data you are searching for? Sep 28, 2021 at 19:59
• Well, does the vcf have gene annotation in it? or rsIDs? Sep 28, 2021 at 23:10

I'm going to try and keep this answer from going overboard while still helping you find your feet. The good news is that it sounds like you have started off with some of this work already done for you, and based upon the files you have above, I will try to indicate what you have already and also where you might be able to go with this. The term you should be entering into Google as the generally accepted term for this pipeline is variant calling or possibly variant curation for the downstream steps.

1. This process starts off with one or more files containing raw observed sequences from a sequencing device (often, but not always, Illumina) This files will usually be in the FASTQ format, but historically I have seen another format called QSEQ. You will likely never see this format and I feel old just bringing it up, but if you ever encounter it, just convert your files to FASTQ immediately. (Files entering here: FASTQ, possibly QSEQ if it was generated well before Carly Rae Jepson suggested that we call her, maybe)
2. Although not a hard requirement, I recommend running something like fastqc or multiqc or some other form of quality control on your reads and making sure that the reads are of satisfactory quality with no anomalous metrics on them. You may or may not decide that you need to do some clean-up on the reads if you determine that there might be adapter contamination or that some reads are partially/entirely garbage quality. (Files entering here: FASTQ, reference genome in FASTA. Files generated: a quality metrics report and possibly a cleaned up FASTQ)
3. Once you have your raw reads and consider them to be of satisfactory quality, they will need to be aligned to a reference genome. Read alignment is a critical, computationally intensive process that is required for many bioinformatics pipelines, meaning that there are many aligners out there that have been optimized for many different situations. If you are running a variant calling pipeline on Illumina short reads from genomic DNA, a current version of BWA should be a solid choice for you here. (Files entering here: FASTQ. Files generated: SAM and/or BAM files with aligned reads)