Sequence Alignment by Information Compression Nacho Caballero

Alignment by Compression

Probability and Information

Traditional Alignments

Traditional Alignments

Traditional alignments can’t handle low complexity regions

AAGCAGAATTTAACATGTGGTTTGCTCATTTGTTCTTTATCGCATCTTTTGAAAACGCTATCGAAATAGCAGTACCTTCAGACTTTTTCCGAATACAGTTTAGCCAAAAATATCAAGAAAAGCTTGAGCGCAAGTTCCTCGAACTTTCTGGACACCCCATTAAACTTTTGTTTGCCGTTAAAAAAGGTACTTATCT !

NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN !

50% of the human genome is masked

Traditional scoring schemes don’t reflect sequence bias

GC content

GC skew

Match +8 Mismatch -4 Gap -3

Traditional alignments lack an objective function to measure quality

Probability and Information

Information and probability are two sides of the same coin

1 .5

.25

.05

4.3 bits

Information

I(event) = log21

p(event)= ! log2 p(event)

1 bit

2 bits

Probability event occurs

Information and probability are two sides of the same coin

1 .5

1 bit

.25

2 bits

Information

Maximum in DNA

Probability event occurs

I(event) = log21

p(event)= ! log2 p(event)

AA

A0 bits

AAAAAAAAAAAAAAAA…

AAAAAAATTTTTTTTT… ATGCACTACTAACGGA…

Compression encodes symbols using a probability distribution

00000000000001101010 11011010

AAAAAACGGG

C A G T C

A G

T

Alignment by Compression

Homologous sequences share information

C A G T

CCGAATCATGTC !CGAATCATTTAGCCAAAAAT…

I(Query)

Markov Expert TAGTAACAGTTTCCGAATCAAGCCAAAAAT !

Homologous sequences share information

C A G T

C A G T

CCGAATCATGTC !CGAATCATTTAGCCAAAAAT…

TAGTAACAGTTTCCGAATCAAGCCAAAAAT !

I(Query| Reference) Mutual Information I(Query)

Markov Expert

Align Expert

Homologous sequences share information

C A

G T

C A G T

C A G T

CCGAATCATGTC !CGAATCATTTAGCCAAAAAT…

I(Query| Reference) Mutual Information I(Query)

Markov Expert

Align Expert

TAGTAACAGTTTCCGAATCAAGCCAAAAAT !

XMAligner wins on distantly related biased sequences

Specificity

Sensitivity

XMAligner is the most sensitive detecting exons

XMAligner detecting a gene cluster

PLASMODIUM GENE CLUSTER

producing better results in distantly related or biased sequences

Alignment by compression overcomes the limitations of traditional alignment