Module5 Session3

Introduc)on
to Bioinforma)cs
Online Course: IBT
Genomics
Compara.ve Genomics
Introduc)on to Bioinforma)cs Online Course:IBT

Genomics| Fatma Guerfali
Learning Objec.ves
Session 3:
Compara.ve Genomics

  Part 1: (intro) Compara)ve Genomics: what is it?
  Part 2: Genomic Varia)on / Compara)ve Genomics: WWWH?
  Part 3: The input
  Part 4: The methods
  Part 5: The output

Learning Outcomes
Session 1:
Compara.ve Genomics

  Navigate through genomic ressources to:
► Retrieve informa)on on a specific gene

(sequence, variants, orthologs…)

► View and interpret genomic alignments

Part 1
(intro)
Compara.ve Genomics:
What is it?

Compara.ve Genomics: a defini.on
Compara)ve genomics is based on the fact that a

genomic varia)on is happening in all organisms.

These changes affects several features in a genome
(structure, organiza)on, func)ons…).

The changes could help monitor evolu)on between
organisms (species…)

Compara)ve genomics deals with the process of

comparing the sequences of whole or parts of
genomes.

Goal:
-‐  iden)fy similari.es and differences between
features in these genomes
-‐  Iden)fy evolu.onary rela.onship between
organisms
Compara)ve genomics : features + evolu.on
ORGANISM A1 ORGANISM A2 ORGANISM B

GENOME A1 GENOME A2 GENOME B
FEATURES A1 FEATURES A2 FEATURE B
Adapted from hTp://receTes-‐aymen.over-‐blog.fr/

hTp://quebueno.be/content/6
Part 2
Genomic Varia.on &

WWWH?

Genomic varia.on : WWWH
WHY ? WHEN ?
WHAT ? HOW ?

WHY ?
Why would a genome evolve ?

WHEN ? à Genomic plas)city allows an organism to:

-‐  adapt to environmental changes
WHAT ?
-‐  Find the best evolu)on path
-‐  Acquire virulence genes, enhanced pathogenicity
HOW ?
-‐  Resistance to drugs
-‐  Increase survival chances of members of a
popula)on
-‐  …

Example : « Genome evolu+on

WHY ? in filamentous
plant pathogens »
WHEN ?
WHAT ?
HOW ?
(Raffaele & Kamoun, 2012)

WHY ?
Factors/events

WHEN ? -‐  Gene transfer
-‐  Environmental pressure for selec)on
-‐ pH
WHAT ?
-‐ temperature
-‐ host
HOW ?
-‐ pathogen
-‐  …
à  A gene)c varia)on could occur in response to such

factors / events
WHY ?
What could be affected ?

WHEN ? -‐  Overall genomic sequence (re-‐arrangements)
-‐  DNA structure
-‐  Regulatory elements
WHAT ?
-‐  Genes size, number, func)on, density
-‐  Nucleo)de composi)on
HOW ?
-‐  …

WHY ?
How could this happen ?

WHEN ? -‐  Large gene)c structural varia)ons (duplica)on, recombina)on…)
-‐  Transposable elements (retrotransposons…)
-‐  Evolu)on of mul)gene families
WHAT ? -‐  Evolu)on of genes with novel func)ons
-‐  Exon shuffling
-‐  Tandem repeats modifica)on
-‐  …
HOW ?

hTp://www.mrschamberlain.com/
WHY ?
How to measure the changes in a genome?

WHEN ? -‐  Sequence varia)on Compara.ve Genomics
-‐  between 2 genomes (1 reference)
-‐  between several genomes
WHAT ?

-‐  Other varia)ons (structure, folding…)
HOW ?


Compara.ve Genomics : WWWH
WHY ? WHEN ?
WHAT ? HOW ?

WHY ?
Why would we compare genomes ?

WHEN ? -‐  Iden)fy evolu)onary history
-‐  Highlight synteny
-‐  Iden)fy genomic rearrangements (large SV events…)
WHAT ?
-‐  Study convergent evolu)on for some organisms (e.g.
virus)
HOW ?
-‐  understand disease outbreak
-‐  Iden)fy pathogenicity markers, drug targets
-‐  …

WHY ?
Why would we compare “por.ons” of genomes ?

WHEN ? -‐  Comparing smaller por)ons of a genome allows to zoom into
regions of genomic re-‐arrangements
WHAT ? -‐  Could be genes: REFERENCE

-‐  Screen for func)onal genes gain A B C
-‐  Screen for func)onal genes loss
A A B C
-‐  Gain of a new func.on
HOW ?
-‐  Exons (length, number…)
-‐  Conserved pathways A E F
-‐  Coding / non-‐coding REFERENCE
A C
-‐  …
C B
A
WHY ?
When do we need to use compara.ve genomics ?

WHEN ? à Establish gene)c and evolu)onary rela)onship
between :

WHAT ?
-‐  En)re organisms
-‐  Sequences
HOW ?

WHY ?
What we generally compare are features of 1 or more
genomes to features of a another genome (reference)
WHEN ?
A genome is complex and composed of different
elements (regulatory, stuctural…)
WHAT ?

In fact, there are different types of DNA features that
HOW ?
can be compared between 2 genomes:
-‐  DNA sequences (small, large, coding/non-‐coding)
-‐  Genes (nature, order…)
-‐  Regulatory elements
-‐  ...
WHY ?
Could be classified in:

WHEN ? -‐ Genome structure

-‐ Genome func.on (coding / non-‐coding)
WHAT ?

-‐ Genome evolu.on
HOW ?

WHY ?
Compara)ve genomics uses Sequence Alignment

WHEN ? Compara)ve genomics is based on Phylogeny that relies
on several key issues:

WHAT ?
-‐  Several genomes are sequenced and available
-‐  Homology between genes (similar func)ons)
HOW ?
-‐  …
àUse complex model genomes to infer knowledge

(Annota.on: func)on…) to unknown or less complex
genomes
WHY ?
Algorithms/programs

WHEN ? in vitro:

-‐  Fluorescence In Situ Hybridiza)on (FISH)
WHAT ?
-‐  Spectral Karyotyping (SKY) and Mul)plex-‐FISH (M-‐
FISH)
HOW ?
-‐  Compara)ve Genomic Hybridiza)on


Keywords in Compara.ve Genomics
THE INPUT THE METHODS THE OUTPUT
DATABASES
INDIVIDUAL GENOME EVOLUTION

SEQUENCE STRUCTURE
PROJECTS ALIGNMENT
FUNCTION
INDIVIDUAL SMALL SCALE
SEQUENCING PROJECTS
ALGORITHMS

Part 3
The input

THE INPUT
Availability of genomes sequenced
Perman, 2014: hTp://blogs.biomedcentral.com/

THE INPUT
Availability of genomes sequenced
hTp://www.ncbi.nlm.nih.gov/genome/browse/
THE INPUT
Availability of databases
hTps://nar.oxfordjournals.org/
hTp://database.oxfordjournals.org/
THE INPUT

« The NCBI Assembly database
(www.ncbi.nlm.nih.gov/assembly/) provides stable
accessioning and data tracking for genome
assembly data (…)
The Assembly database reports metadata such as
assembly names, simple sta)s)cal reports of the
assembly (number of con)gs and scaffolds,
con)guity metrics such as con)g N50, total sequence
length and total gap length) as well as the assembly
update history. The Assembly database also tracks
the rela<onship between an assembly submi?ed to
the Interna<onal Nucleo<de Sequence Database
Consor<um (INSDC) and the assembly represented
in the NCBI RefSeq project. Users can find
assemblies of interest by querying the Assembly
Resource directly or by browsing available
assemblies for a par<cular organism. Links in the
Assembly Resource allow users to easily download
sequence and annota+ons for current versions of
genome assemblies from the NCBI genomes FTP site»
hTps://nar.oxfordjournals.org/
THE INPUT

« Background: Early classifica+on of prokaryotes
was based solely on phenotypic similari+es, but
modern prokaryote characteriza+on has been
strongly influenced by advances in gene+c methods.
With the fast development of the sequencing
technology, the ever increasing number of genomic
sequences per species offers the possibility for
developing distance determina<ons based on
whole-‐genome informa<on. The average nucleo+de
iden+ty (ANI), calculated from pair-‐wise
comparisons of all sequences shared between two
given strains, has been proposed as the new metrics
for bacterial species defini<on and classifica<on.
Results: In this study, we developed the web version
of ANItools (hRp://ani.mypathogen.cn/), which helps
users directly get ANI values from online sources. A
database covering ANI values of any two strains in a
genus was also included (2773 strains, 1487 species
and 668 genera) »
THE INPUT
File formats
Different file formats may be accepted

Blast (NCBI) accepts: FASTA
-‐  Fasta sequence
-‐  simple sequence
-‐  Accession Number
-‐  Local file from disk
GenBank
(megablast)
Whole sequence
(or subsequence) Accession

THE INPUT
File formats
hTp://blast.ncbi.nlm.nih.gov/
THE INPUT
File formats
THE INPUT
File formats
THE INPUT
File formats
Part 4
The methods

THE METHODS
Sequence Alignment for DNA
DNA sequence alignment consists of aligning 2 DNA

sequences in order to iden)fy regions showing
sequence similarity

This highlights regions showing rela)onship in
terms of:
-‐  Evolu)on
-‐  Structure
-‐  Func)on
THE METHODS
For simple sequences:

Compare ATCTTCGTTG and ATCTCGTATG
GAP
ATCT T
CGT -‐ TG
ATCT -‐
CGT ATG

GAP

THE METHODS
For sequences that are not as simple :

-‐  long sequences
-‐  more complex sequences (divergent…)
-‐  large number of sequences
-‐  …

à need Algorithms !

THE METHODS
2 key approaches

-‐  Global Alignment
à Op)mizes the alignment to span the ATCATTCGTTGACTGTG
A
-‐ -‐ -‐ T T
-‐ G
-‐ T GAC
-‐ -‐ TG
full length of sequences that are aligned.

-‐  Local Alignment
à Op)mizes the alignment to take into ATCATTCGTTGACTGTG
-‐ -‐ -‐ A TT
-‐ G
-‐ T GACTG
-‐ -‐
account regions of the highest similarity
between divergent sequences.

THE METHODS
Algorithms efficiency and choice depends on the number of

sequences to compare

Pairwise Alignment
Sequence alignment of 2 sequences
à Output: func)on, structure, evolu)onary rela)onship
Mul.ple sequence Alignment

Sequence alignment of 3 or more sequences (same length)
à Output: homology, evolu)onary rela)onship

THE METHODS
Pairwise Alignment
A Pairwise Alignment is an op)mized local or global alignment of
2 sequences.
-‐  3 methods:
-‐  Dot-‐matrix
-‐  Dynamic programming
-‐  Word-‐based

NB: Efficiency can be reduced in low complexity regions (repe++ve sequences…)
Can be evaluated by the MUM (Maximum Unique Match)
à Long MUM sequences = more related sequences

THE METHODS
Pairwise Alignment
INSERTION INTO QUERY
Dot-‐matrix method R: AB
Q: AIB
-‐  2 sequences (A and B) are

aligned using a 2-‐dimensional
matrix INVERTION INTO QUERY
R: ABC
-‐  Iden)ty is shown with a dot Q: AB’C
-‐  Diagonal shows high similarity
à Dot plot of the sequence R REARRANGEMENT

INTO QUERY
against sequence Q R: ABCDE
Q: AFCBE
Adapted from hTp://mummer.sourceforge.net/manual/AlignmentTypes.pdf
THE METHODS
Pairwise Alignment
Dynamic programming can

-‐  Use a scoring matrix
-‐  Assign a match score (+), a mismatch score (-‐), and a gap
penalty (-‐).
-‐  Use two different gap penal)es for opening a gap and for
extending a gap (gap opening >>> gap extension)
à generally results in less gaps in an alignment and gaps are
grouped together = more biological relevance.

Different algorithms for Global and Local Alignments
hTps://en.wikipedia.org/wiki/Sequence_alignment#cite_note-‐mount-‐1
THE METHODS
Pairwise Alignment
Dynamic programming

-‐  Global Alignment
à Needleman–Wunsch algorithm.

-‐  Local Alignment
à Smith–Waterman algorithm.

THE METHODS
Pairwise Alignment
Global Alignment
à Needleman–Wunsch
algorithm.

hTps://en.wikipedia.org/wiki/Needleman–Wunsch_algorithm
THE METHODS
Pairwise Alignment
Local Alignment
à Smith-‐Waterman algorithm.

hTps://en.wikipedia.org/wiki/Smith–Waterman_algorithm
THE METHODS
Pairwise Alignment
Word-‐based method

-‐  Op)mal alignment not garanteed, but efficient and faster
than dynamic programming
-‐  Useful for databases searches
-‐  « words » are small por)ons (length k) of the query sequence
that are used to screen the database

à Ex: BLAST

Adapted from different web resources

THE METHODS
Pairwise Alignment

-‐  BLAST (Basic Local Alignment Search Tool)
-‐  Algorithm to compare a query sequence to a library or database
of sequences
-‐  Allows to es)mate iden)ty with a certain confidence threshold
-‐  Popular in the scien)fic community ()me efficiency…)

THE METHODS
Pairwise Alignment QUERY

ATCATTCGTTGACTGTG
k=11
ATCATTCGTTG
-‐  BLAST TCATTCGTTGA
► The query sequence can be filtered to CATTCGTTGAC
exclude low-‐complexity regions ATTCGTTGACT
► Seeding: list all possible words of length TTCGTTGACTG
(DNA: default k=11) TCGTTGACTGT
CGTTGACTGTG
► Search database for matching words using a
scoring matrix = calculate the match score
► A threshold score is evaluated to top-‐rank DATABASE ATCATTCGTTG
ATTCGTTGACT
the most similar sequences
TCGTTGACTGT
► Process repeated for all words of the query CGTTGACTGTG
THE METHODS
Pairwise Alignment

-‐  BLAST
► Best match is followed by an extension in both direc.on, with scoring
► Extension con)nued only if the alignment is above the threshold
► The con)guous alignment without gaps (now possible) and a higher score
is the HSP (High Scoring Segment Pair)
QUERY ATCATTCGTTGACTGTG
ATCATTCGTTG
DATABASE ATCATTCGTTGACTGTG ATTCGTTGACT
TCGTTGACTGT
EXTENSION EXTENSION CGTTGACTGTG
HSP Introduc)on to Bioinforma)cs Online Course:IBT

THE METHODS
Pairwise Alignment

-‐  BLAST
► A scoring matrix is used to evaluate the quality of the alignment
► A scoring matrix is a predefined subs)tu)on matrix (match = 1,
mismatch = 0…)
► ex: BLOSUM

THE METHODS

THE METHODS

THE METHODS
Pairwise Alignment
-‐  BLAST output
 A list of sequences that have the best match to the query

THE METHODS
Pairwise Alignment
  e-‐value: probability that the alignment is found by chance
(the lower the e-‐value, the more interes)ng the match)

THE METHODS
Pairwise Alignment
  Alignment details : sequences (query and database) aligned
with % iden)ty…)

THE METHODS
Pairwise Alignment

-‐  BLAST have different variant queries according to the type of
query sequence (Q) and type of sequence in the database (R):

Q R
BLASTN Nucleic Acid à Nucleic Acid
BLASTX Translated Nucleic Acid à Protein
TBLASTX Translated Nucleic Acid à Translated Nucleic Acid
TBLASTN Protein à Translated Nucleic Acid
BLASTP Protein à Protein

THE METHODS
Mul.ple Sequence Alignment

Mul.ple Sequence Alignment have been developed to handle
more than 2 sequences at a )me.

Align all queried sequences to form a query group.

Allows to iden)fy conserved sequences por)ons among a
group of queried sequences that are:
-‐ known to be evolu)onarily related
-‐ of unknown/supposed evolu)onar rela)onship à this
mul)ple alignment helps to establish their evolu)onar
rela)onships (phylogene)c trees)
THE METHODS

Different methods:
-‐  Dynamic programming

-‐  Progressive method
-‐  Itera)ve method : HMMs (Hidden Markov Models)
-‐  …

à Evalua.on of Conserva.on across sequences

THE METHODS

Dynamic programming

-‐ Op)mized for 2 sequences, so computa)onally expensive here
-‐  Extends the sequence matrix from 2 sequences to the number
of sequences in the query : alignment between pairs of
sequences
à MSA

THE METHODS

Progressive method

-‐  Aligns sequences to iden)fy the most similar ones
-‐  Then progressively adds all other related sequences of the
group
à Clustal (clustal-‐Omega: medium-‐large alignments)

à T-‐Coffee (small alignments)


THE METHODS

Progressive method
Clustal
PAIRWISE ALIGNMENT GUIDE MULTIPLE SEQUENCE
SEQUENCES & DISTANCE MATRIX TREE ALIGNMENT
A A
B B
C
C
D
D
SIMILARITY
THE METHODS

HMMs

-‐  Determine Probability scores for mul)ple sequence alignments
-‐  The aligned sequences serves as a group, no need to previously order the
sequences
-‐  Can build an HMM profile
-‐  Improved for more distant sequences
hTp://www.cbs.dtu.dk
THE METHODS

Conserva.on scores

-‐  Based on the fact that the highest conserva)on is maintained through
evolu)on for the most important func)ons (promoters, essen)al enzymes,
exons…)
-‐  Regulatory regions might be generally evolving « faster »
-‐  Mul)ple alignments à iden)fy what elements reject subs.tu.ons

(subs.tu.ons occur in neutral DNA, do not occur if an element is
func.onally constrained)
THE METHODS

Conserva.on scores

-‐  PhyloP (Phylogene)c p-‐values)
Measures Base Conserva)on from non-‐coding regions

-‐  PhastCons (part of PHAST: PHylogene)c Analysis
with Space/Time models)
Measures Base Conserva)on based on HMM model

-‐  GERP (Genomic Evolu)onary Rate Profiling)
Measures Base Conserva)on to es)mate the neutral evolu)on rate in genomes

-‐  SiPhy (SIte-‐specific PHYlogene)c analysis)
Models the paTern of subs)tu)on (biased nucleo)de subs)tu)on, HMM)
(Gerber et al., 2009)
THE METHODS

Conserva.on scores

(Pheasant and Mauck, 2007)
THE METHODS
Whole Genome Alignment
MUMmer Ultra-‐fast alignment of large-‐scale DNA

(hTp://mummer.sourceforge.net)
-‐ Alignment of en)re genomes (complete or draw)
-‐ Maximal Unique Matcher: Find the MUMs = subsequences that occur
only once in both genomes compared and not extendable anymore
-‐ Suffix-‐tree based approach

WebACT Artemis Comparison Tool (ACT)
(www.webact.org)
Visualize the alignment of publically available prokaryo)c genomes

Databases: Ensembl, VISTA

Part 5
The output

THE OUTPUT
Genomic Structure
Analyzing a genome structure means to analyze:

► At the Genome level
-‐  Base composi)on (%GC, codon bias, nucleo)de distribu)on…)
-‐  Genome organiza)on (SV events, genomic rearrangements…)
-‐  Sequence conserva)on (regulatory elements, repe))ve regions…)
-‐  Synteny (conserved or not)
► At the Gene level

-‐  Gene order

THE OUTPUT
Genomic Func.on
Analyzing func)ons in a genome means to analyze:

► At the non-‐coding sequence level
-‐  Regulatory func)ons…
► At the coding sequence level

à  Insights into func)ons
-‐  Compare gene sequences
-‐  Compare protein-‐coding por)ons
à  How ?
Different algorithms help iden)fy por)ons of the genome coding for proteins
-‐  Ab ini+o approaches
-‐  Using homology … hTp://www.cbs.dtu.dk
THE OUTPUT
Genomic Evolu.on
From the Mul)ple sequence alignments we can infer homology

and es)mate the evolu)on distance between sequences/
organisms.

Analysis could be:
-‐  Based on en)re Genome comparisons
-‐  Based on Gene comparisons
-‐  …

THE OUTPUT
Genomic Evolu.on
Based on en.re genome comparison

-‐  Phylogene)c rela)onship between organisms
-‐  Previous dogma:

"Anything found to be true of E. coli must also be true of elephants"
(Jacques Monod, 1954)

à  Need to be related to its phylogene)c context !!
à  Different outputs expected depending if :
à  Comparing closely related species
à  Comparing evolu)onarily distant species
THE OUTPUT
Genomic Evolu.on: in easy words
COMPARING CLOSELY
RELATED SPECIES
COMPARING EVOLUTIONARILY
DISTANT SPECIES
hTp://www.beller.no
hTp://www.notcot.org/
Compara.ve Genomics and Genome
Evolu.on in easy words
COMPARING CLOSELY
RELATED SPECIES
COMPARING EVOLUTIONARILY
DISTANT SPECIES
A: NOT SPICY B: SPICY

C: NOT SPICY
Adapted from hTp://receTes-‐aymen.over-‐blog.fr/
hTp://quebueno.be/content/6
THE OUTPUT
Genomic Evolu.on

Examining the dynamics of closely related genomes helps to build therapeu)c
strategies for Ebola virus:

-‐  Ebola virus largest outbreak (2014)
-‐  Comparison of 100 available Ebolavirus (Filiviridae) genomes to each other +
to other viral genomes.
-‐  Filoviridae are different from all other viral genomes
-‐  Filovirus genomes : sequence diversity but proteins with similar func)ons
and gene order
à  Ebolavirus genomes very similar but different in intergenic regions and
genes of specific func)on = poten)al vaccine candidates.
(Jun et al., 2015)
THE OUTPUT
Genomic Structure
Gene)c map of the UPEC strain 536 chromosome
(Brzuszkiewicz et al., 2006)

THE OUTPUT
Genomic Structure
Whole Genome Comparison of
(A) all strains
(B) Enterobacter
(C) Erwinia
(D) Pantoea
(Lòpez-Fernàndez et al., 2015)

THE OUTPUT
Genomic Evolu.on
Phylogene.c rela.onships

« rela+onship of the Malassezia genus
with respect to other fungi with
sequenced genomes.»

G: gene family gain; L: gene family loss
(Wu et al., 2015)

THE OUTPUT
Genomic Evolu.on

-‐  Synteny
► Defined as the overall conserva)on of (gene/blocks) order in chromosomes
between different genomes.

► Evaluated in whole genomes, blocks could include large por)ons of genomes.

► Recombina)on / crossing over affects groups of adjacent genes in a
chromosome à linkage group.
THE OUTPUT
Genomic Evolu.on
Based on en.re

genome comparison
Synteny
(Jaillon et al., 2004)

THE OUTPUT
Genomic Evolu.on
Based on en.re

genome comparison
Synteny
(Jaillon et al., 2004)

THE OUTPUT
Genomic Evolu.on
Based on individual

gene comparison GENE DUPLICATION

Homology
2 genes are homologs if they ORTHOLOGS ORTHOLOGS
have a common ancestor

PARALOGS
They can be classified in
orthologs and paralogs:

à  As a consequence of
specia)on = Orthology

à  As a consequence of HOMOLOGS
duplica)on = Paralogy hTp://www.notcot.org/

THE OUTPUT
Genomic Evolu.on
Based on individual gene comparison

Orthology

Finding orthologs can be the first step in whole genome alignment
à  BLAST Reciprocal Best Hit (best pairs of orthologs)

à  OrthoMCL (possible predic)ons for several species)
à  EnsemblCompara (precomputed data): orthology and paralogy predic)ons
based on phylogenies.
à  eggNOG (evolu)onary genealogy of genes: Non-‐supervised Orthologous
Groups):OGs of proteins across different taxonomic levels

THE OUTPUT
Genomic Evolu.on
Based on individual gene comparison

Inferring Annota.on: Ontologies

Assigning func)ons to Genes:
GO (Gene Ontology)
à  Biological Process

à  Molecular Func.on
à  Cellular Component
The GO database contains different tools

to retrieve these informa)ons.
(Hu et al., 2007)
hTp://geneontology.org/
THE OUTPUT
Genomic Evolu.on
Func.onal/Structural Predic.ons

► impact of a muta.on on the func.on
Analysis of the impact of aa subs)tu)on
à  Strutural and/or Func)onal effect of single point muta)ons SNPs
-‐  PolyPhen-‐2 (hTp://gene)cs.bwh.harvard.edu/pph2/…)
-‐  SIFT (hTp://siw.jcvi.org)
-‐  VEP (hTp://www.ensembl.org/Homo_sapiens/Tools/VEP)

► impact of the muta.on on the Struture
Impact on gene coding por)ons (gain/loss) or non-‐coding por)ons

THE OUTPUT
Browsers
VISTA
(hip://genome.lbl.gov/vista/index.shtml)
Collec)on of resources for compara)ve
genomics

VISTA browers can be used to analyze
pre-‐computed alignments or user
generated or queried sequences

VISTA servers
-‐  mVISTA (query sequences vs mul)-‐species sequences)
-‐  rVISTA (iden)fica)on of regulatory TF binding sites)
-‐  gVISTA (query sequences vs whole-‐genome assemblies)
-‐  wgVISTA (alignment of 10Mb sequences (finished/draw): microbes…) …
VISTA tools: Rviewer region viewer to compare genomic intervals

THE OUTPUT
Browsers
Ensembl Browser
(hTp://www.ensembl.org)

► Compara)ve analyses at the genome
and gene levels
► Genome sequences compared using
pairwise and mul)ple whole-‐genome
alignments
► These alignments help to determine
-‐  Synteny
-‐  Sequence conserva)on scores
-‐  Gene homology rela)onships (GeneTrees)
(Herrero et al., 2015)

Compara.ve genomics
Take-‐home messages
Input / Output
► DNA Sequences (genome, gene…)
► Homology, similarity, evolu)onary distance

Alignment
► Whole genome : MUMmer…
► Mul)ple genomes : MGA…
► Mul)ple Sequence Alignment : Clustal…
► Global/Local Sequence Alignment : BLAST…

Input / Output files
► Fasta/GenBank to alignment or phylogene)c distances


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Introduc)on

Introduc)on to Bioinforma)cs Online Course:IBT

Introduc)on to Bioinforma)cs Online Course:IBT

► Retrieve informa)on on a speciﬁc gene

Introduc)on to Bioinforma)cs Online Course:IBT

Introduc)on to Bioinforma)cs Online Course:IBT

Compara)ve genomics is based on the fact that a

Introduc)on to Bioinforma)cs Online Course:IBT

Compara)ve genomics deals with the process of

Compara)ve genomics : features + evolu.on

ORGANISM A1 ORGANISM A2 ORGANISM B

Adapted from hTp://receTes-­‐aymen.over-­‐blog.fr/

Genomic Varia.on &

Introduc)on to Bioinforma)cs Online Course:IBT

Introduc)on to Bioinforma)cs Online Course:IBT

Introduc)on to Bioinforma)cs Online Course:IBT

Example : « Genome evolu+on

(Raﬀaele & Kamoun, 2012)

à A gene)c varia)on could occur in response to such

Introduc)on to Bioinforma)cs Online Course:IBT

Introduc)on to Bioinforma)cs Online Course:IBT

Introduc)on to Bioinforma)cs Online Course:IBT

Introduc)on to Bioinforma)cs Online Course:IBT

WHAT ? -­‐ Could be genes: REFERENCE

Introduc)on to Bioinforma)cs Online Course:IBT

Introduc)on to Bioinforma)cs Online Course:IBT

àUse complex model genomes to infer knowledge

Introduc)on to Bioinforma)cs Online Course:IBT

THE INPUT THE METHODS THE OUTPUT

INDIVIDUAL GENOME EVOLUTION

Introduc)on to Bioinforma)cs Online Course:IBT

Introduc)on to Bioinforma)cs Online Course:IBT

Availability of genomes sequenced

Perman, 2014: hTp://blogs.biomedcentral.com/

Availability of genomes sequenced

Availability of databases

Availability of databases

Availability of databases

Diﬀerent ﬁle formats may be accepted

Introduc)on to Bioinforma)cs Online Course:IBT

Sequence Alignment for DNA

DNA sequence alignment consists of aligning 2 DNA

Sequence Alignment for DNA

For simple sequences:

Introduc)on to Bioinforma)cs Online Course:IBT

Sequence Alignment for DNA

For sequences that are not as simple :

Introduc)on to Bioinforma)cs Online Course:IBT

Sequence Alignment for DNA

Introduc)on to Bioinforma)cs Online Course:IBT

Sequence Alignment for DNA

Algorithms eﬃciency and choice depends on the number of

Mul.ple sequence Alignment

Introduc)on to Bioinforma)cs Online Course:IBT

Sequence Alignment for DNA

Sequence Alignment for DNA

-­‐ 2 sequences (A and B) are

à Dot plot of the sequence R REARRANGEMENT

Sequence Alignment for DNA

Adapted from hTp://receTes-‐aymen.over-‐blog.fr/

à  A gene)c varia)on could occur in response to such

WHAT ? -‐  Could be genes: REFERENCE

-‐  2 sequences (A and B) are

-‐  Dynamic programming

à Clustal (clustal-‐Omega: medium-‐large alignments)

-‐  Regulatory regions might be generally evolving « faster »

-‐  Mul)ple alignments à iden)fy what elements reject subs.tu.ons

MUMmer Ultra-‐fast alignment of large-‐scale DNA

-‐  Previous dogma: