Sequence logo

A sequence logo showing the most conserved bases around the initiation codon from all human mRNAs (Kozak consensus sequence). Note that the initiation codon is not drawn to scale, otherwise the letters AUG would each have a height of 2 bits.

In bioinformatics, a sequence logo is a graphical representation of the sequence conservation of nucleotides (in a strand of DNA/RNA) or amino acids (in protein sequences).[1] A sequence logo is created from a collection of aligned sequences and depicts the consensus sequence and diversity of the sequences. Sequence logos are frequently used to depict sequence characteristics such as protein-binding sites in DNA or functional units in proteins.

Overview

A sequence logo consists of a stack of letters at each position. The relative sizes of the letters indicates their frequency in the sequences. The total height of the letters depicts the information content of the position, in bits.

Logo creation

To create sequence logos, related DNA, RNA or protein sequences, or DNA sequences that have common conserved binding sites, are aligned so that the most conserved parts create good alignments. A sequence logo can then be created from the conserved multiple sequence alignment. The sequence logo will show how well residues are conserved at each position: the higher the number of residues, the higher the letters will be, because the better the conservation is at that position. Different residues at the same position are scaled according to their frequency. The height of the entire stack of residues is the information measured in bits. Sequence logos can be used to represent conserved DNA binding sites, where transcription factors bind.

The information content (y-axis) of position ${\displaystyle i}$ is given by:[2]

for amino acids, ${\displaystyle R_{i}=\log _{2}(20)-(H_{i}+e_{n})}$
for nucleic acids, ${\displaystyle R_{i}=\log _{2}(4)-(H_{i}+e_{n})}$

where ${\displaystyle H_{i}}$ is the uncertainty (sometimes called the Shannon entropy) of position ${\displaystyle i}$

${\displaystyle H_{i}=-\sum f_{a,i}\times \log _{2}f_{a,i}}$

Here, ${\displaystyle f_{a,i}}$ is the relative frequency of base or amino acid ${\displaystyle a}$ at position ${\displaystyle i}$, and ${\displaystyle e_{n}}$ is the small-sample correction for an alignment of ${\displaystyle n}$ letters. The height of letter ${\displaystyle a}$ in column ${\displaystyle i}$ is given by

${\displaystyle {\text{height}}=f_{a,i}\times R_{i}}$

The approximation for the small-sample correction, ${\displaystyle e_{n}}$, is given by:

${\displaystyle e_{n}={\frac {1}{\ln {2}}}\times {\frac {s-1}{2n}}}$

where ${\displaystyle s}$ is 4 for nucleotides, 20 for amino acids, and ${\displaystyle n}$ is the number of sequences in the alignment.

Consensus logo

A consensus logo is a simplified variation of a sequence logo that can be embedded in text format. Like a sequence logo, a consensus logo is created from a collection of aligned protein or DNA/RNA sequences and conveys information about the conservation of each position of a sequence motif or sequence alignment[1][3] . However, a consensus logo displays only conservation information, and not explicitly the frequency information of each nucleotide or amino acid at each position. Instead of a stack made of several characters, denoting the relative frequency of each character, the consensus logo depicts the degree of conservation of each position using the height of the consensus character at that position.

A sequence logo for the LexA-binding motif of several Gram-positive species.
A consensus logo for the LexA-binding motif of several Gram-positive species.