BIOINFORMATICS

Margaret O. Dayhoff

edited the collection of amino acid sequences compiled in the Atlas of protein sequence and structure by comparison of amino acid sequences by developing computer software for detecting distantly related sequences

EMBL

established data library in 1980

NCBI

established in USA and became the primary information databank and provider of information

Bioinformatics

combination of biology and informatics

In silico

analysis by computer

Human Genome Project

spurred the rapid rise of bioinformatics as a formal discipline

NCBI

creates automated systems for storing and analyzing knowledge about molecular biology, biochemistry and genetics

Identity

extent to which two sequences are the same

Alignment

lining up two or more sequences to search for maximal regions of identity or similarity

Local alignment

alignment of some portion of two sequences

Multiple sequence

alignment of three or more sequences arranged with gaps so common residues align together

Optimal alignment

alignment of two sequences with the best degree of identity

Conservation

sequence changes that maintain the properties of the original sequence

Similarity

relatedness of sequences, percent identity or conservation

Algorithm

fixed set of commands in a computer program

Domain

discreet portion of a protein or DNA sequence

Motif

highly conserved short region in protein domains

Gap

space introduced in alignment to compensate for insertions or deletions

Homology

similarity attributed to descent from a common ancestor

Orthology

homology in different species due to a common ancestral gene

Paralogy

homology within the same species resulting from gene duplication

Query

sequence presented for comparison with all other sequences in a selected database

Annotation

description of functional structures such as introns or exons in DNA

Interface

point of meeting between a computer and an external entity

GenBank

genetic sequence database sponsored by the National Institutes of Health

PubMed

search service sponsored by the National Library of Medicine providing access to literature citations in Medline and related databases

SwissProt

protein database sponsored by the Medical Research Council United Kingdom

International Union of Pure and Applied Chemistry and International Union of Biochemistry and Molecular Biology

organizations that made the IUB universal nomenclature for mixed bases

R

purine or A and G

Y

pyrimidine or C and T

M

A and C

K

G and T

S

C and G

W

A and T

H

A, C, T or not G

B

C, G, T or not A

V

A, C, G or not T

D

A, G, T or not C

N

A, C, G, T or any

X or ?

unknown A or C or G or T

O or -

deletion

BLAST

Basic Local Alignment Search Tool

BLAST

used for homology searches

BLAST

searches GenBank maintained by NCBI

BLAST

searches for regions of local similarity between protein and nucleotide sequences

E-value

number of matches to the query sequence

Very low E-values 10^-12

associated with perfect match

Mis-primes

caused by multiple potential binding sites

Off-target products

caused by multiple potential binding sites

GenBank

international nucleotide sequence database and repository of NCBI

ENA

international nucleotide sequence database and repository of EMBL-EBI

DDBJ

nucleotide sequence database in Japan

UniProt

protein database with sequence and functional annotation

Ensembl

vertebrate and eukaryotic genomes database

Ensembl genomes

genome-scale data for bacteria, protists, fungi, plants and invertebrate metazoa

InterPro

functional analysis database for protein sequences

Pfam

manually curated collection of protein domain families

FASTA

most widely used format in bioinformatics

.fasta or .fa

file extensions for FASTA

FASTA

format beginning with greater than symbol >

GenBank file

starts with LOCUS and sequence itself

ORIGIN

beginning of sequence in GenBank format

//

ending of GenBank sequence

EMBL file

used by European Molecular Biology Laboratory

ID

identifier marking beginning of EMBL file

SQ

start of sequence in EMBL format

.aln

typical file extension for CLUSTAL

CLUSTAL

multiple sequence alignment format used for phylogenic algorithms

Dashes -

indicate deletions in CLUSTAL

.nex or .nxs

typical file extensions for NEXUS

NEXUS

begins with wording “nexus” followed by blocks containing commands

.phy or .ph

typical file extensions for PHYLIP

Sequence alignment

arranging DNA, RNA or protein sequences to identify regions of similarity

Reference sequence

known sequence

Query sequence

unknown sequence

Global alignment

uses Needleman-Wunsch algorithm

Global alignment

assumes sequences are similar over entire length

Local alignment

based on Smith-Waterman

Local alignment

finds local regions with highest similarity

Pairwise sequence alignment

used by BLAST

Dot matrix

old method of producing pairwise alignments

Dynamic programming algorithm

advanced method of producing pairwise alignments

Word or K-tuple method

advanced method used in FASTA and BLAST

Dot plots

another term for dot matrix

Richard Bellman

introduced dynamic programming method in 1940

Word or K-tuple method

identifies short non-overlapping subsequences of query sequence

BLASTp

compares amino acid query sequence against protein database

BLASTn

compares nucleotide query sequence against nucleotide database

BLASTx

searches six frame translation products of nucleotide sequence against protein database

tBLASTn

searches protein sequence against translated nucleotide sequence database

tBLASTx

compares six frame translations of nucleotide query against six frame translations of database

Mega BLAST

optimized for aligning long DNA sequences

PSI BLAST

position specific iterated BLAST

PHI BLAST

pattern hit initiated BLAST

Nucleotide BLAST

option clicked first when performing BLAST procedure

CCAGAGTCCAGCTGCTGCTCATACTACTGATACTGCTGGG

example sequence used for BLAST practice

BLASTn

program selected under program selection category during procedure

E-value less than 1.0

indicates significant alignments

Percent identity

percentage similarity between query and subject sequence

Accession number

unique identifying number assigned to a sequence before database entry