Hernn DopazoLaboratorio de Genmica Biomdica y EvolucinLab 25. Pab II. FCEyN. UBA.CONICET

Junio 2012

Bioinformtica y Genmica

Claves para la Nueva Biologa

Cambio de Paradigma Tecnolgico

Produccin Artesanal Cambio Tecnolgico Produccin Industrial

Datos Genticos (~1980) Datos Genmicos (~2005)

Tsunami de Datos Genticos

Qu hacemos realmente ?

Kit Bsico de Recursos Bioinformticos

Apuntes sobre la Nueva Biologa

Ecologa y Gentica de Poblaciones

Filogeografa y Ecologa de Poblaciones

Filogeografa y Ecologa de Poblaciones

Modelos de Aprendizaje y Evolucin

Filogenmica

SNPs Enfermedades

Seleccin Natural en Genomas Completos

Filoma Humano

Desarrollo de Software

Seleccin Natural en Mdulos de Funciones

Filogenmica y Modelos de Evolucin

Filogenmica en Virus

Complete 454 genome sequencing

and phylogenomic analysis

Complexity and Information Theory A widely accepted measure of relative complexity is

the minimum amount of information required to specify the ontogeny and operation of a system.

The information content or complexity of an object can be measured by the length of its shortest description.

For instance the string 01010101010101010101010101 has the short description 13 repetitions of 01, while 11001000011000011101111011 has no simpler description other than writing down the string itself.

The minimum genome sizes observed across metazoa show a consistent increase with complexity from simple nematode worms to insects to vertebrates.

This holds true for both biochemical and genome sequence measurements, as well as for computationally compressed genome sizes.

BioEssays 29:288299, 2007

1- Burrows-Wheeler transform (BWT) The transform is done by sorting all rotations of

the text in lexicographic order, then taking the last column.

2- Move-To-Front transform (MTF)

The MTF is a way to encode a string, that most of the times it allows to represent the same string in a more compact way than its original form.

The main idea is that each symbol in the data is replaced by its index in the stack of recently used symbols.

3- Entropy : -sum {i=0}^3 p(i) * log 4 p(i) ;

Measuring Complexity Definition:

Given a string s we define complexity ratio,

CR (s) = Entropy (MTF (BWT (s) ) )

0 CR 1; CV (s) = CR * length (s)

Example 1. Sequences with CR=0 have the simplest combinatorial structure: they contain just one symbol. Rotations in lexicographic order (A)

9 A|AAAAAAAAA 8 AA|AAAAAAAA 7 AAA|AAAAAAA 6 AAAA|AAAAAA 5 AAAAA|AAAAA 4 AAAAAA|AAAA 3 AAAAAAA|AAA 2 AAAAAAAA|AA 1 AAAAAAAAA|A 0 AAAAAAAAAA|

BWT(s) = AAAAAAAAAAMTF(BWT(s)) = 0,0,0,0,0,0,0,0,0,0CR(s) = E(MTF(BWT(s))) = 0

Example 2. If a sequence contains just half of the symbols then CR is at most 0.5Let s=AAAAAACCAC Rotations in lexicographic order (A, C)

0 AAAAAACCAC|1 AAAAACCAC|A2 AAAACCAC|AA3 AAACCAC|AAA4 AACCAC|AAAA8 AC|AAAAAACC5 ACCAC|AAAAA9 C|AAAAAACCA7 CAC|AAAAAAC6 CCAC|AAAAAA

BWT(s) = CAAAACAACAMTF(BWT(s)) = 0,1,0,0,0,1,1,0,1,1CR(s) = E(MTF(BWT(s))) = 0.500

Example 3. The de Bruijn sequence with the lowest CR among all de Bruijn sequences of order 2 in the four letter alphabet: s= AACCTTCGTAGCATGG

Rotations in lexicographic order (A, C, G, T)

0 AACCTTCGTAGCATGG|1 ACCTTCGTAGCATGG|A9 AGCATGG|AACCTTCGT12 ATGG|AACCTTCGTAGC11 CATGG|AACCTTCGTAG2 CCTTCGTAGCATGG|AA6 CGTAGCATGG|AACCTT3 CTTCGTAGCATGG|AAC15 G|AACCTTCGTAGCATG10 GCATGG|AACCTTCGTA14 GG|AACCTTCGTAGCAT7 GTAGCATGG|AACCTTC8 TAGCATGG|AACCTTCG5 TCGTAGCATGG|AACCT13 TGG|AACCTTCGTAGCA4 TTCGTAGCATGG|AACC

BWT(s) = GATCGATCGATCGTACMTF(BWT(s)) = 0,1,2,3,3,3,3,3,3,3,3,3,3,2,3,3CR(s) = E(MTF(BWT(s))) = 0.593

Example 4. The de Bruijn sequence with the highest CR among all de Bruijn sequences of order 2 in the four letter alphabet: s=AACCATAGTTGCTCGG

Rotations in lexicographic order (A, C, G, T)

0 AACCATAGTTGCTCGG|1 ACCATAGTTGCTCGG|A6 AGTTGCTCGG|AACCAT4 ATAGTTGCTCGG|AACC3 CATAGTTGCTCGG|AAC2 CCATAGTTGCTCGG|AA13 CGG|AACCATAGTTGCT11 CTCGG|AACCATAGTTG15 G|AACCATAGTTGCTCG10 GCTCGG|AACCATAGTT14 GG|AACCATAGTTGCTC7 GTTGCTCGG|AACCATA5 TAGTTGCTCGG|AACCA12 TCGG|AACCATAGTTGC9 TGCTCGG|AACCATAGT8 TTGCTCGG|AACCATAG

BWT(s) = GATCCATGGTCAACTGMTF(BWT(s)) = 0,1,2,3,0,2,2,3,0,1,3,3,0,1,2,3CR(s) = E(MTF(BWT(s))) = 0.989

Human Language Complexity

Torquato Tasso. Johann Wolfgang von Goethe. German

Divina Commedia. Dante Alighieri. Italian

Principia Mathematica. Isaac Newton. Latin

El Quijote. Miguel de Cervantes. Spanish

Complete Works. W. Shakespeare. English

Coefficients: Estimate Std. Error t value Pr(>|t|) (Intercept) -4.457e+03 1.660e+04 -0.269 0.794 size 3.781e-01 8.019e-03 47.149 4.35e-12 ***

Multiple R-squared: 0.996, Adjusted R-squared: 0.9955 F-statistic: 2223 on 1 and 9 DF, p-value: 4.349e-12

Cuentos de amor, locura y muerte. Horacio Quiroga. Spanish

Origin of Species. Charles Robert. Darwin. English

Facundo. Domingo F. Sarmiento. Spanish

Les Miserables. Victor Hugo. French

The Human Genome. Scientific Abstract. English

El Aleph- Jorge Luis Borges. Spanish

Lenght (Log L)

Hum

an L

angu

age

Com

plex

ity (

Log

MFT

E)

104 105 106

104

105

106

Genome Diversity (54 sps)Features Species Taxa

LGS Monodelphis domestica MammalsHomo sapiens MammalsPongo abelii MammalsMacaca mulatta MammalsPan troglodytes MammalsMus musculus MammalsRattus norvegicus MammalsBos taurus MammalsEquus caballus MammalsCanis familiaris Mammals

AP RP Zea mays Plants

AP Danio rerio FishesTaeniopygia guttata BirdsGallus gallus Birds

AP Sorghum bicolor Plants

AP Oryzias latipes Fishes

AP Physcomitrella patens Bryophyta

AP Populus trichocarpa Plants

AP Oryza sativa Plants

AP Brachypodium distachyon PlantsAnopheles gambiae InvertebratesApis mellifera Invertebrates

AP Tetraodon nigroviridis Fishes

AP Arabidopsis lyrata Plants

GE Daphnia pulex InvertebratesDrosophila melanogaster Invertebrates

AP, RG Arabidopsis thaliana PlantsTribolium castaneum InvertebratesCaenorhabditis elegans Invertebrates

LGS: Largest Genome Sequenced

SGS: Shortest Genome Sequenced

AP: Ancient Polyploid

RP: Recent Polyploid

LBG: Largest Bacterial Genome

SBG: Shortest Bacterial Genome

IBP: Intracellular Bacterial Parasite

RG: Reduced Genome

GE: Gene Expansion

EE: Extreme Environment

UE: Unicellular Eukaryote

SSD: Single-Strand DNA

DSD: Double-Strand DNA

RNA: RNA Virus

SL: Synthetic Life

Features Species Taxa

Ciona intestinalis Urochordate

UE Dictyostelium discoideum Amebozoa

UE Thalassiosira pseudonana Heterokonta

UE Phaeodactylum tricornutum Heterokonta

UE Plasmodium falciparum Ampicomplexa

AP Saccharomyces cerevisiae Fungi

LBG Burkholderia xenovorans Bacteria

Escherichia coli Bacteria

Mycobacterium tuberculosis Bacteria

Bacillus subtilis Bacteria

EE Sulfolobus islandicus Archaea

EE Methanocaldococcus vulcanius Archaea

EE Thermococcus sibiricus Archaea

SL Synthetic mycoplasma mycoides Bacteria

IBP, RG Ureaplasma urealyticum Bacteria

IBP, RG Buchnera aphidicola Bacteria

IBP, RG, SBG Carsonella ruddii Bacteria

DSD Human herpesvirus1 Virus

DSD Enterobacteria phage lambda Phage

RNA Sudan ebolavirus Virus

RNA HIV 1 Virus

SSD Enterobacteria phage m13 Phage

SSD Tomato mosaic Virus

RNA Hepatitis B Virus

SGS, RNA Hepatitis D Virus

Genome Size (Log S)

Gen

ome

Com

plex

ity (L

og M

TFE

)

104

105

106

107

108

109

104 105 106 107 108 109

Taxa

Virus

Phage

Bacteria

Archaea

Fungi

Ampicomplexa

Heterokonta

Amebozoa

Urochordate

Invertebrates

Plants

Fishes

Bryophita

Birds

Mammals

HIV virus

Sudan Ebola virus

Human Herpes virus

Buchnera aphidicola Ureaplasma urealyticum

Escherichia coli

Plasmodium falciparumSaccharomyses cerevisiaeDictyostelium dicoideumPhaedodactylum tricornutum

Caenorahbditis. elegans

Tetraodon nigroviridis

Physcomitrella patens

Gallus gallus

Ciona intestinalis

Lambda phage

M13 phage

Thermococcus sibiricus

Daphnia pulex

Burkholderia xenovorans

Zea mays

Synthetic Mycoplasma mycoides

M. domestica

Sulfolobus islandicus

Hepatitis D virus

Tomato mosaic virusHepatitis B

GCR

Carsonela ruddii

Genome ComplexityFull set (54 sps)Coefficients: Estimate Std. Error t value Pr(>|t|) (Intercept) -9.115e+06 1.848e+07 -0.493 0.624 size 9.673e-01 1.517e-02 63.750 |t|) (Intercept) -1.279e+06 1.513e+06 -0.845 0.403 size 9.888e-01 1.150e-03 859.732 |t|) (Intercept) 9.165e+07 4.357e+07 2.103 0.0617 . size 6.332e-01 5.571e-02 11.367 4.85e-07 ***

Multiple R-squared: 0.9282, Adjusted R-squared: 0.921 F-statistic: 129.2 on 1 and 10 DF, p-value: 4.855e-07 ------------------------------------------------------------- Linear Model * Interaction