Multiple Alignment Format

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MafIndex

Biopython provides an interface for fast access to the multiple alignment of several sequences across an arbitrary interval: for example, chr10:25,079,604-25,243,324 in mm9. As MAF files are available for entire chromosomes, they can be indexed by chromosome position and accessed at random. This functionality is available in the class MafIO.MafIndex.

Creating or loading a MAF index

Indexes are created by determining the chromosome start and end position for a specific sequence name (generally a species), which must appear in every alignment block in the file. In whole-genome alignments generated by Multiz, the chromosome of one species is generally used as the reference to which other species are aligned. This reference species will appear in every block, and should be used as the target_seqname parameter. For UCSC multiz files, the form of species.chromosome is used.

To index a MAF file, or load an existing index, create a new MafIndex object. If the index database file sqlite_file does not exist it will be created, otherwise it will be loaded.

from Bio.AlignIO import MafIO.MafIndex

idx = MafIO.MafIndex(sqlite_file, maf_file, target_seqname)

Retrieving alignments overlapping a given interval

The search(starts, ends) generator function accepts a list of start and end positions, and yields MultipleSeqAlignment objects that overlap the given intervals. This is particularly useful for obtaining alignments over the multiple exons of a single transcript, eliminating the need to retrieve an entire locus.

results = idx.search([25079604], [25243324])

for multiple_alignment in results:
    print multiple_alignment

Retrieving a pre-spliced alignment over a given set of exons

The get_spliced(starts, ends, strand = "+") function accepts a list of start and end positions representing exons, and returns a single MultipleSeqAlignment object of the in silico spliced transcript from the reference and all aligned sequences. If part of the sequence range is not found in a particular species in the alignment, dashes ("-") are used to fill the gaps, or "N"s if the sequence is not present in the reference (target_seqname) sequence. If strand is opposite that in the reference sequence, all sequences in the returned alignment will be reverse complemented.

# convert the alignment for mouse Foxo3 (NM_019740) from MAF to FASTA

from Bio.AlignIO import MafIO.MafIndex
from Bio import SeqIO
import sys

idx = MafIO.MafIndex("chr10.mafindex", "chr10.maf", "mm9.chr10")

multiple_alignment = idx.get_spliced([41905591, 41916271, 41994621, 41996331],
                                     [41906101, 41917707, 41995347, 41996548],
                                     strand = "+")

for seqrec in multiple_alignment:
    SeqIO.write(seqrec, sys.stdout, "fasta")

Example

chr10:7,350,034-7,383,048) In this example, we are going to download the 30-way alignment of various species to mouse chromosome 10, generate an index file, and load the multiple alignment across the Pcmt1 locus.

The MAF file is available at: http://hgdownload.cse.ucsc.edu/goldenPath/currentGenomes/Mus_musculus/multiz30way/maf/chr10.maf.gz

from Bio.AlignIO import MafIO.MafIndex as MafIndex

idx = MafIndex("chr10.mafindex", "chr10.maf", "mm9.chr10")

idx

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