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 hacer de cada organismo un ser vivo. Genómica Se le llama así al proceso que lleva a la caracterización total del material genético de un organismo Genómica Datos genómicos Bioinformatica
Secuenciación Bases de datos
Transcriptoma Análisis de secuencias Proteoma Análisis datos Metaboloma ….ómicos
Automatización procesos 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 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 ow and dependencies in metagenome an
Its really complex
and full of pitfalls Data Microbial genomes analysis: the signs before the f published per year
Completely sequenced 14Mio and published Early growth linear
microbial genomes followed by
exponential ORFs from increase complete genomes vs metagenomics ORFs
Technical issues Sampling +preparati Sequencing method Assembly+annotatio Coverage ….. 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 15 from more than a dozen phyla 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 90% of the orthologous groups were found. 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(0 Specific enrichments. Protein function prediction in metagenomics samples
Neighborhood Blast NextKnown to Known NextUnknown to Unknown No Prediction No Hit 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.200
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 Chromosome 10, chitin biosynthesis. 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.
