slides - Bioinformatics Sannio

Bioinformatics
introduction
Luigi Cerulo
University of Sannio
Informatics and Biology
Why informatics is important for biology?
(love or interest?)
Erwing
Schrödinger
“
... life is the process of storage,
retrieving, and transmission of
biological information.
Central dogma of molecular biology
replication
replication
transcription
DNA
RNA
reverse
transcription
translation
Protein
Central dogma of molecular biology
replication
replication
transcription
DNA
RNA
reverse
transcription
Watson & Crick
1962 Nobel (medicine)
translation
Protein
Central dogma of molecular biology
replication
Roger D. Kornberg
2006 Nobel (chemistry)
replication
transcription
DNA
RNA
reverse
transcription
Watson & Crick
1962 Nobel (medicine)
translation
Protein
Central dogma of molecular biology
replication
Roger D. Kornberg
2006 Nobel (chemistry)
replication
transcription
DNA
translation
RNA
reverse
transcription
Watson & Crick
1962 Nobel (medicine)
Andrew Z. Fire, Craig C. Mello
2006 Nobel (medicine)
Protein
Central dogma of molecular biology
replication
Roger D. Kornberg
2006 Nobel (chemistry)
replication
transcription
DNA
V. Ramakrishnan, T. A. Steitz, A. E. Yonath
2009 Nobel (chemistry)
translation
RNA
reverse
transcription
Watson & Crick
1962 Nobel (medicine)
Andrew Z. Fire, Craig C. Mello
2006 Nobel (medicine)
Protein
Central dogma of molecular biology
replication
E.H. Blackburn, C.W. Greider, J.W.. Szostak
2009 Nobel (medicine)
Roger D. Kornberg
2006 Nobel (chemistry)
replication
transcription
DNA
V. Ramakrishnan, T. A. Steitz, A. E. Yonath
2009 Nobel (chemistry)
translation
RNA
reverse
transcription
Watson & Crick
1962 Nobel (medicine)
Andrew Z. Fire, Craig C. Mello
2006 Nobel (medicine)
Protein
Information can be:
created
transformed
destroyed! (not for matter)
L’informazione esiste in quanto supportata o
trasmessa da un supporto fisico
Information support of a cell
Computational Systems
Artificial
Natural
Human Genome
about 3,200 million of base pairs
Wellcome Collection Museum in London
Il genoma umano è lungo circa
1.1 metri
Contiene circa 3 miliardi di basi
Il tutto è impacchettato in uno
Human Genome
about 3,200 million of base pairs
Wellcome Collection Museum in London
Il genoma umano è lungo circa
1.1 metri
Contiene circa 3 miliardi di basi
Il tutto è impacchettato in uno
fits on 4
floppy disk
fits on 1
cd rom
Bioinformatics
•
Analysis
Bioinformatics (Paulien Hogeweg,
1970)
study of informatic processes in biotic systems
•
Biophysics
•
Biochemistry
You continued working
I
on topics related to molecuthe st
lar biology but how did the
your m
sequencing era affect your readays
search?
H
Hogeweg: At the bestarte
ginning of the 80s, the first
aroun
public data sets became
main
available. So we got indeed
cused
this very first set from the
pheno
EMBL and one of the very
that
first things we did was to
was s
create a multiple alignment
that
programme. It was actualcould
Hogeweg anno 1980
ly the first programme of
inform
this kind [J Mol Evol, 20:175-86]. It basiquence could not.
cally worked by generating a provisional
our hypercycle wor
phylogenetic tree, by clustering sequences
tern formation in s
based on pairwise alignments. Then, the
next step was aligning sequences progresI am aware that
sively along the tree, to obtain a multiple
portant in your res
Meaning now
•
Bioinformatics is a research discipline aimed at
resolving biological problems at molecular level by
mean of computational approaches (and statistics).
Il panda è un carnivoro
o un erbivoro?
è stato carnivoro
perchè si è scoperto
che nel panda il gene
T1R1 (responsabile
della digestione della
carne) è silente
Gli algoritmi di allineamento sono i principali strumenti forniti
dalla bioinformatica per confrontare genomi appartenenti a
specie diverse
: Biology’s Unifying Theme
ented
is a
Earth
d by
ms
as
ch
hing
time
re and
e very
ar and
on
atively
ee of
h an
her
o
and
milkare
its.
Giant panda
Spectacled bear
Ancestral
bear
Sloth bear
Sun bear
Common ancestor
of all modern bears
American black bear
Asiatic black bear
Common ancestor of
polar bear and brown bear
Polar bear
Brown bear
30
25
20
15
10
5
Millions of years ago
Figure 1.10 An evolutionary tree of bears. This tree is a hypothesis (a tentative
model) based on both the fossil record and a comparison of DNA sequences among
▲
DNA sudoku
• Su doku
• L’algoritmo per risolvere il sudoku è stato
ideato 2000 anni fa in Cina
• Recentemente è stato usato per
assemblare il DNA
Altri algoritmi
• Kabsch algorithm (Allineamento 3D di proteine)
• Baum–Welch algorithm (Risoluzione dei modelli Markoviani e ricerca
di motivi all’interno di un genoma)
• K-means clustering algorithm (Analisi di dati da microarray)
• Needleman–Wunsch algorithm (Allineamento globale di sequenze)
• Smith-Waterman algorithm (Allineamento locale di sequenze)
• Robinson-Foulds algorithm (Distanza tra genomi per ricostruire gli
alberi filogenetici)
• Ukkonen's algorithm (Alberi di suffisso per la ricerca veloce di
sequenze all’interno di un database)
A huge amount of bioinformatics tools?
A huge amount of bioinformatics tools?
Need we others?
A huge amount of bioinformatics tools?
?
?
?
Yes, because
technology evolves
new biological problems
…
Demand for Bioinformaticians profiles
•
Basic
just adopts available tools
•
Intermediate
develops simple
bioinformatics pipelines
•
Advanced
develops new tools
Experiments, in vivo, in vitro, ... in silico
The paradigm shift
The Human
genome
completed
Mendel
establish the
laws of
inheritance
1859
C. Darwin
publish
“Origin of
Specie”
1865
1953
J. Watson &
F. Crick
determine
the structure
of DNA
double helix
2001
The Scientific method
New Problem
Hypothesis/Theory
prediction
proof
deductive
reasoning
experimental
observations
inductive
reasoning
Research in biology (some years ago...)
New Problem
Hypothesis/Theory
prediction
proof
deductive
reasoning
experimental
observations
inductive
reasoning
Research in biology (Now...)
New Problem
Hypothesis/Theory
prediction
proof
deductive
reasoning
experimental
observations
inductive
reasoning
1953
2015
Social impact (now)
Personalized medicine
(It is a reality now)
•
Personal Genome Project
farmacogenomica
nutrigenomica
…
Steve Jobs, co-founder of Apple
Inc., was one of the first 20 people
in the world to have his DNA
sequenced, for which he paid
$100,000.
Social impact (far future)
•
Synthetic life
•
Genome manipulation
•
…