Clase2 2010 4junio

GENÓMICA Y BIOINFORMÁTICA.
lunes 7 de junio de 2010

Frecuentemente se relaciona el genoma
con “el libro de la vida”. Esta analogía se
debe a que ambos pueden ser leídos
secuencialmente, de principio a fin, una
letra tras otra, y porque en el genoma se
encuentra la información necesaria para

Genómica
Se le llama así al proceso que
lleva a la caracterización total del
material genético de un
organismo

Genómica
Bioinformatica
Datos genómicos
Bases de datos
Secuenciación
Análisis
de secuencias
Transcriptoma
Análisis datos
….ómicos
Proteoma
Automatización
procesos
Metaboloma

GENÓMICA
GENÓMICA GENÓMICA
COMPARATIVA ESTRUCTURAL
GENÓMICA
FUNCIONAL

GENÓMICA ESTRUCTURAL
Estudia la estructura
tridimensional de las
macromoléculas especialmente
proteínas y ácidos nucleicos, y
las funciones asociadas a ella.

GENÓMICA ESTRUCTURAL
 Estos estudios incluyen también :
-Organización de las secuencias dentro los

genomas.
-Asignación de loci.
-Resolución de mapas cromosómicos.
-Mapeo físico de genes.
-Secuenciación.
-Uso de mapas genómicos para el análisis de
genes

GENÓMICA COMPARATIVA
Es la información conocida de un organismo que
puede ser utilizada para obtener información de
otro.
Ejemplo:
-Alineamientos
-Búsqueda de motivos
-Análisis filogenético
-Predicción de estructura de proteínas

GENÓMICA FUNCIONAL
Campo de la biología molecular que se
propone utilizar la vasta acumulación de
datos producidos por los proyectos de
genómica (como los "proyectos genoma"
de los distintos organismos) para
describir las funciones e interacciones
entre genes (y proteínas).

A diferencia de la genómica y la
proteómica, la genómica funcional se
centra en los aspectos dinámicos de los
genes, como su transcripción, la
traducción las interacciones proteína-
proteína, en oposición a los aspectos
estáticos de la información genómica
como la secuencia del ADN o su
estructura.

Bioinformática
 Permitan manipular la información contenida en
estas bases de datos se hace indispensable.
 Caracterización y clasificación de nuevos genes

y proteínas
 Métodos que faciliten la identificación de los

elementos encargados de la regulación de los
diferentes elementos genómicos
 Determinen la historia evolutiva, la función y los

determinantes estructurales.

Ejemplos
 Genomica comparativa: Minimal gene set
y metagenomic comunities

Las proteínas homólogas comparten un ancestro común

Micoplasma genitalium “the Haemophilus influenzae
smallest among known cellular 1703 coding genes
life forms 468 coding genes Gram negative
Gram positive
Minimal set of
genes requeridos
para la vida
“Extrapolation between genomes will then

most likely accelerate the definition of what
amounts to a “parts catalog” of cellular components
in a large number of organisms”. Bernhard Palsson,
NATURE BIOTECHNOLOGY VOL 18 NOVEMBER 2000

22 genes con desplazamiento no-ortólogo
262 genes en común
6 genes parásito-específicos
256 genes considerados como el conjunto mínimo

Workflow and dependencies in metagenome analysis
Its really complex

and full of pitfalls!

Data analysis: the signs before the flood
Completely sequenced
and published Early linear growth
followed by exponential
microbial genomes increase

Microbial genomes Data analysis: the signs before the flood
published per year
350k 500k 750k 1.5Mio
2003 2004 2005 2006

No of ORFs in all genomes (incl. ours)
2003 2004 2005 2006

Microbial genomes Data analysis: the signs before the flood
published per year
14Mio
ORFs from
complete
genomes vs
metagenomics
ORFs
1.1Mio 1.5Mio
350k 500k 750k 1.5Mio
2003 2004 2005 2006

¿Por qué 16S?
 Its presence in almost all bacteria, often
existing as a multigene family, or operons.
 The function of the 16S rRNA gene over time

has not changed, suggesting that random
sequence changes are a more accurate measure
of time (evolution).
 The 16S rRNA gene (1,500 bp) is large enough

for informatics purposes

Comparative metagenomics
Increase of functional assignments (via
orthologous groups) with coverage
Reason for differences
Biological issues
Orthologous groups (COGs + NOGs)
GC content
Genome sizes
Phylogeny
Evolutionary speed
Evenness/Richness
Functionality
Technical issues
Sampling +preparation
Sequencing method
Assembly+annotation
Coverage
…..
Tringe*, von Mering* … Bork, Hugenholtz, Rubin Science 308(05)554
Whale fall samples
Soil DNA • Between 25 and150 distinct
ribotypes
*At least 847 distinct ribotypes
• The most abundant accounts for
from more than a dozen phyla
15 to 25%
*More than 3000 predicted
• Between 100 and 700 Mbp would
bacterial ribotypes
be needed to generate a draft
assembly for the most prevalent
*Less than 1% of the nearly
genome
150,000 reads exhibited overlap
*Between two and five billion bp

would be necessary to obtain the
eightfold coverage
Acid mine drainage biofilm
A wide diversity of bacteria, few community
archaeal species, and some fungi
and unicellular eukaryotes were
found. 90% of the orthologous groups were
detected with just 25 Mbp of raw sequence

Functional profiling of microbial communities.
These profiles clearly suggest that the predicted protein complement of a

community is similar to that of other communities whose environments of
origin pose similar metabolic demands.
-These profiles clearly suggest that the predicted protein complement of a
community is similar to that of other communities whose environments of origin
pose similar metabolic demands.
-Our results further support the hypothesis that the Bfunctional[ profile of a
community is influenced by its environment and that EGT data can be used to
develop fingerprints for particular environments.
Tringe*, von Mering* et al. Science 308(05)554

Specific
enrichments.

Protein function prediction in metagenomics samples
Blast
Known Unknown No Hit

Neighborhood
Next to Known Next to Unknown No Prediction

Neighbor-based predictions possible for almost 30% of 1.25 Mio ORFs studied
More than 75,000 would not have been possible by homology

Neighbor-based predictions possible for almost 30% of 1.25 Mio ORFs studied
More than 75,000 would not have been possible by homology
Overall function predictions for >75% of environmental data!
Our functional knowledge: glass half full or half empty?
Function prediction in gene families of 1.5Mio proteins from 4 environments
Our knowledge concentrates in

large, well established families
contributing 65% of the ORFs;
However, many specialized
functions in small gene families
are to be discovered
All against all, MCL clustering,

(60bits, inflation factor 1.1)
Harrington et al, PNAS Aug.2007

RNA interference:
listening to the sound of silence

776 genes are enriched in the ovary 98%
A large proportion was 429 no-letales 362 Sin fenotipo Over half the
required for either egg 322 letales 389 con fenotipo genes tested
production or ------------------ ---------------------- showed at least
embryogenesis 751 totales 751 totales one detect enable
phenotype
Most commonly
embryonic lethality
209 fenotipo post-embriónico
180 fenotipo pre-embriónico
67 post embriónico no letal ----------------------------------------
322 post embriónico esteril and letal 389 con fenotipo
------------------------------------
389 con fenotipo

Finding relationships between embryonic lethality, degree
of conservation, and extent of enriched expression in the
ovary
¿Los genes que participantes en la embriogenesis estan altamente conservados?

Correlation between RNAi Phenotypic
Classes and Expression Levels in the
Ovary for the Set of 751 Genes Tested
No-phenotype
Post-embryonic
Partial
Strong

Genes giving rise to embryonic lethal phenotype
were under-represented in the X chromosome
Expected based on # of genes

Expected based on distribution
Observed
1, unknown;
2, RNA transcription/modification;
3, chromatin/chromosome structure;
4, cell cycle control;
5, protein synthesis/folding/translocation/degradation;
6, energy metabolism;
7, Signal transduction/differentiation;
8, cytoskeleton associated or component;
9, Nuclear-cytoplasmic transport; a
10, chitin biosynthesis.

1, unknown;
2, RNA transcription/modification;
3, chromatin/chromosome structure;
4, cell cycle control;
5, protein synthesis/folding/translocation/degradation;
6, energy metabolism;
Phenoclusters
7, Signal transduction/differentiation;
8, cytoskeleton associated or component;
9, Nuclear-cytoplasmic transport; a
10, chitin biosynthesis.
Chromosome
No visible biology
Exagerated Defect in the Granular Or DNA
Few eggs asyncrony First 50 min cytoplasm replication
Genes predicte to function in Genes involved in mRNA procesing

chromosome biology or DNA replication
The resulting ‘phenoclusters’ can provide information about both the
involvement of genes in particular modules and the functional relationships
that might exist between them

Clustering algorithms were used to group genes with similar expression
profiles, and these groups were visualized as ‘mountains’ in a ‘topomap’.

Proteínas ampliamente distribuidas con función
variada relacionadas con respuesta a estres

DNA damage response (DDR) protein interaction map for C. elegans. Arrows represent yeast two-hybrid
(Y2H) interactions and nodes (circles) represent proteins. Blue and orange nodes indicate products of genes from the DNA
repair and checkpoint phenoclusters, respectively. mrt-2 and C04F12.3 belong to a common phenocluster, and their
products physically interact in the Y2H system
Damage recovery module.
The nodes represent proteins and the lines represent yeast two-hybrid (Y2H) interactions.
All of the six proteins were identified as required for methyl methanesulfonate (MMS)
resistance in phenotypic analyses

Core germline interactome map for C. elegans.
The nodes represent proteins and the lines

represent yeast two-hybrid (Y2H)
interactions. The interactome map
was integrated with transcriptome
and phenome data.
Red lines indicate:
a) interactions between proteins whose

corresponding genes have both
b) similar expression profiles and
c) overlapping RNA interference (RNAi)

phenotypes.

A systems biology strategy
Starting from one known component, more components involved in a module of interest can be
identified, for example, by interactome mapping. A network can be constructed to describe
these interactions. Perturbation experiments are then systematically performed and responses
from the rest of the network are recorded, for example, by transcriptome profiling.


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GENÓMICA Y BIOINFORMÁTICA.

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

 Estos estudios incluyen también :

-Organización de las secuencias dentro los

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

 Caracterización y clasificación de nuevos genes

 Métodos que faciliten la identificación de los

 Determinen la historia evolutiva, la función y los

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

“Extrapolation between genomes will then

lunes 7 de junio de 2010

lunes 7 de junio de 2010

Its really complex

lunes 7 de junio de 2010

lunes 7 de junio de 2010

350k 500k 750k 1.5Mio

2003 2004 2005 2006

lunes 7 de junio de 2010

2003 2004 2005 2006

lunes 7 de junio de 2010

 The function of the 16S rRNA gene over time

 The 16S rRNA gene (1,500 bp) is large enough

lunes 7 de junio de 2010

*Between two and five billion bp

lunes 7 de junio de 2010

These profiles clearly suggest that the predicted protein complement of a

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

Next to Known Next to Unknown No Prediction

lunes 7 de junio de 2010

Our knowledge concentrates in

All against all, MCL clustering,

Harrington et al, PNAS Aug.2007

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

¿Los genes que participantes en la embriogenesis estan altamente conservados?

lunes 7 de junio de 2010

lunes 7 de junio de 2010

Expected based on # of genes

lunes 7 de junio de 2010

Genes predicte to function in Genes involved in mRNA procesing

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

lunes 7 de junio de 2010

The nodes represent proteins and the lines

a) interactions between proteins whose

b) similar expression profiles and

c) overlapping RNA interference (RNAi)

lunes 7 de junio de 2010

lunes 7 de junio de 2010