Data Analysis in the Terminal

Quality Control

Quaulity Check With Fastqc

To get help,

$ fastqc --help
            FastQC - A high throughput sequence QC analysis tool

SYNOPSIS

    fastqc seqfile1 seqfile2 .. seqfileN

    fastqc [-o output dir] [--(no)extract] [-f fastq|bam|sam]
           [-c contaminant file] seqfile1 .. seqfileN

DESCRIPTION

    FastQC reads a set of sequence files and produces from each one a quality
    control report consisting of a number of different modules, each one of
    which will help to identify a different potential type of problem in your
    data.

    If no files to process are specified on the command line then the program
    will start as an interactive graphical application.  If files are provided
    on the command line then the program will run with no user interaction
    required.  In this mode it is suitable for inclusion into a standardised
    analysis pipeline.

    The options for the program as as follows:

    -h --help       Print this help file and exit

    -v --version    Print the version of the program and exit

    -o --outdir     Create all output files in the specified output directory.
                    Please note that this directory must exist as the program
                    will not create it.  If this option is not set then the
                    output file for each sequence file is created in the same
                    directory as the sequence file which was processed.

    --casava        Files come from raw casava output. Files in the same sample
                    group (differing only by the group number) will be analysed
                    as a set rather than individually. Sequences with the filter
                    flag set in the header will be excluded from the analysis.
                    Files must have the same names given to them by casava
                    (including being gzipped and ending with .gz) otherwise they
                    won't be grouped together correctly.

    --nano          Files come from naopore sequences and are in fast5 format. In
                    this mode you can pass in directories to process and the program
                    will take in all fast5 files within those directories and produce
                    a single output file from the sequences found in all files.

    --nofilter      If running with --casava then don't remove read flagged by
                    casava as poor quality when performing the QC analysis.

    --extract       If set then the zipped output file will be uncompressed in
                    the same directory after it has been created.  By default
                    this option will be set if fastqc is run in non-interactive
                    mode.

    -j --java       Provides the full path to the java binary you want to use to
                    launch fastqc. If not supplied then java is assumed to be in
                    your path.

    --noextract     Do not uncompress the output file after creating it.  You
                    should set this option if you do not wish to uncompress
                    the output when running in non-interactive mode.

    --nogroup       Disable grouping of bases for reads >50bp. All reports will
                    show data for every base in the read.  WARNING: Using this
                    option will cause fastqc to crash and burn if you use it on
                    really long reads, and your plots may end up a ridiculous size.
                    You have been warned!

    -f --format     Bypasses the normal sequence file format detection and
                    forces the program to use the specified format.  Valid
                    formats are bam,sam,bam_mapped,sam_mapped and fastq

    -t --threads    Specifies the number of files which can be processed
                    simultaneously.  Each thread will be allocated 250MB of
                    memory so you shouldn't run more threads than your
                    available memory will cope with, and not more than
                    6 threads on a 32 bit machine

    -c              Specifies a non-default file which contains the list of
    --contaminants  contaminants to screen overrepresented sequences against.
                    The file must contain sets of named contaminants in the
                    form name[tab]sequence.  Lines prefixed with a hash will
                    be ignored.

    -a              Specifies a non-default file which contains the list of
    --adapters      adapter sequences which will be explicity searched against
                    the library. The file must contain sets of named adapters
                    in the form name[tab]sequence.  Lines prefixed with a hash
                    will be ignored.

    -l              Specifies a non-default file which contains a set of criteria
    --limits        which will be used to determine the warn/error limits for the
                    various modules.  This file can also be used to selectively
                    remove some modules from the output all together.  The format
                    needs to mirror the default limits.txt file found in the
                    Configuration folder.

   -k --kmers       Specifies the length of Kmer to look for in the Kmer content
                    module. Specified Kmer length must be between 2 and 10. Default
                    length is 7 if not specified.

   -q --quiet       Supress all progress messages on stdout and only report errors.

   -d --dir         Selects a directory to be used for temporary files written when
                    generating report images. Defaults to system temp directory if
                    not specified.

BUGS

    Any bugs in fastqc should be reported either to simon.andrews@babraham.ac.uk
    or in www.bioinformatics.babraham.ac.uk/bugzilla/
$ cd RNA-Seq/QC/Fastqc_Out

Code For Few Samples

$ fastqc -t 4  --outdir  ~/RNA-Seq/QC/Fastqc_Out RNA-Seq/RAW_Data/3290-TM-0001-18_S18_L002_R1_001-2.fastq.gz RNA-Seq/RAW_Data/3290-TM-0001-18_S18_L004_R1_001-2.fastq.gz

Code For Many Samples

Note

If your raw data path names end with .fastq change the *.fastq.gz to *.fastq in the following code.

$ for f in ~/RNA-Seq/RAW_Data/*.fastq.gz; do fastqc --outdir  ~/RNA-Seq/QC/Fastqc_Out -t 4 $f  ; done

Explanation

$ for f in ~/RNA-Seq/RAW_Data/*.fastq.gz;

Note

This will pick any file that has file extension .fastq.gz in the /home/yourusername/RNA-Seq/RAW_Data directory.

Then,

$ do fastqc --outdir  ~/RNA-Seq/QC/Fastqc_Out -t 4 $f

Note

will execute fastqc on each file in the /home/yourusername/RNA-Seq/RAW_Data until there is no more .fastq.gz files left in that directory.

$ cd ~/ #Go back to home directory

Adapter Trimming with scythe

$ scythe --help
Usage: scythe -a adapter_file.fasta sequence_file.fastq
Trim 3'-end adapter contaminants off sequence files. If no output file
is specified, scythe will use stdout.

Options:
  -p, --prior               prior (default: 0.300)
  -q, --quality-type        quality type, either illumina, solexa, or sanger (default: sanger)
  -m, --matches-file        matches file (default: no output)
  -o, --output-file output trimmed sequences file (default: stdout)
  -t, --tag         add a tag to the header indicating Scythe cut a sequence (default: off)
  -n, --min-match   smallest contaminant to consider (default: 5)
  -M, --min-keep    filter sequnces less than or equal to this length (default: 35)
  --quiet           don't output statistics about trimming to stdout (default: off)
  --help            display this help and exit
  --version         output version information and exit

  Information on quality schemes:
  phred                     PHRED quality scores (e.g. from Roche 454). ASCII with no offset, range: [4, 60].
  sanger            Sanger are PHRED ASCII qualities with an offset of 33, range: [0, 93]. From
                    NCBI SRA, or Illumina pipeline 1.8+.
  solexa            Solexa (also very early Illumina - pipeline < 1.3). ASCII offset of
                    64, range: [-5, 62]. Uses a different quality-to-probabilities conversion than other
                    schemes.
  illumina          Illumina output from pipeline versions between 1.3 and 1.7. ASCII offset of 64,
                    range: [0, 62]

Unzip your data before this step,

gzip -d Code For few Samples

$ gzip -d RNA-Seq/RAW_Data/3290-TM-0001-18_S18_L002_R1_001-2.fastq.gz
$ gzip -d RNA-Seq/RAW_Data/3290-TM-0001-18_S18_L004_R1_001-2.fastq.gz

Note

Your outputs will be under RNA-Seq/RAW_Data/

gzip -d Code For Many Samples

Note

You have to be in your HOME directory to issue following commands. If are not in your HOME do,

$ cd ~/

to go back to your HOME.

$ for f in RNA-Seq/RAW_Data/*.gz; do gzip -d  $f  ; done

Scythe Code For Few Samples

$ scythe  -a RNA-Seq/Adaptors/TruSeq_adapters.fasta  -M 50 -o RNA-Seq/QC/Adapter_Removed/Adapt_rem_3290-TM-0001-18_S18_L002_R1_001-2.fastq RNA-Seq/RAW_Data/3290-TM-0001-18_S18_L002_R1_001-2.fastq

$ scythe  -a RNA-Seq/Adaptors/TruSeq_adapters.fasta  -M 50 -o RNA-Seq/QC/Adapter_Removed/Adapt_rem_3290-TM-0001-18_S18_L004_R1_001-2.fastq  RNA-Seq/RAW_Data//3290-TM-0001-18_S18_L004_R1_001-2.fastq

Scythe Code For Many Samples

$ for f in RNA-Seq/RAW_Data/*.fastq; do scythe -a RNA-Seq/Adaptors/TruSeq_adapters.fasta -o RNA-Seq/QC/Adapter_Removed/Adapt_rem_${f##*/}   $f  ; done

Quality Trimming with sickle

sickle se --help
Usage: sickle se [options] -f <fastq sequence file> -t <quality type> -o <trimmed fastq file>

Options:
-f, --fastq-file, Input fastq file (required)
-t, --qual-type, Type of quality values (solexa (CASAVA < 1.3), illumina (CASAVA 1.3 to 1.7), sanger (which is CASAVA >= 1.8)) (required)
-o, --output-file, Output trimmed fastq file (required)
-q, --qual-threshold, Threshold for trimming based on average quality in a window. Default 20.
-l, --length-threshold, Threshold to keep a read based on length after trimming. Default 20.
-x, --no-fiveprime, Don't do five prime trimming.
-n, --trunc-n, Truncate sequences at position of first N.
-g, --gzip-output, Output gzipped files.
--quiet, Don't print out any trimming information
--help, display this help and exit
--version, output version information and exit
$ sickle se -q 20  -t sanger -f RNA-Seq/QC/Adapter_Removed/Adapt_rem_3290-TM-0001-18_S18_L002_R1_001-2.fastq  -o RNA-Seq/QC/Trimmed/Q_trimmed_3290-TM-0001-18_S18_L002_R1_001-2.fastq

Sickle Code For Many Samples

$ for f in RNA-Seq/QC/Adapter_Removed/*.fastq; do sickle se -q 20  -t sanger  -f $f -o RNA-Seq/QC/Trimmed/Q_trimmed_${f##*/} ; done

Short-reads Alignment with Tophat2

Indexing your Genome

To make bowtie2 indexes for your Genome,

$ cd RNA-Seq/Reference/Genome/
$ gzip -d Gmax_275_v2.0.gz
$ mv Gmax_275_v2.0 Gmax_275_v2.0.fa
$ bowtie2-build Gmax_275_v2.0.fa Gmax_275_v2.0

Warning

THIS WILL TAKE LONG TIME

Aligning Short Reads

To align short reads to Genome using Tophat2,

$ cd ~/RNA-Seq
$tophat2 --num-threads 4  --output-dir RNA-Seq/Alignment/Tophat2 RNA-Seq/Reference/Genome/Gmax_275_v2.0 RNA-Seq/QC/Trimmed/Q_trimmed_3290-TM-0001-18_S18_L002_R1_001-2.fastq

Tophat2 Code For Many Samples

$for f in RNA-Seq/QC/Trimmed/*.fastq; do  tophat2 --num-threads 4  --output-dir RNA-Seq/Alignment/${f##*/} RNA-Seq/Reference/Genome/Gmax_275_v2.0  $f; done

Excercise

  1. Run Cufflinks2 on alignment file(SAM)