Refbio Fase II Refbio Fase II

Marcos J. Araúzo Bravo Head of Computational Biology and Systems Biomedicine Group

Head of Computational Biology Data Analysis Platform

Datos de salud para salud

13-September-2018

Congreso de Salud Digital:

Conectando la Salud

marcos.arauzo@biodonostia.org

mararabra@yahoo.co.uk

Discovering the NON pluripotency of human adult Germ Stem Cells

Important to share data: Free omics data allows discover biology research errors

Objectives of use of Big data in health

Unknown

triggers

Integration

Big data

Discovery

Omics

Molecular

mechanism

Clinica

Comprehensive understanding of disease

Important to develop data processing tools

Alan Turing (1912-54) Enigma

Bombe

TF

The cell nucleus as a Turing Machine

P3BSseq: Parallel processing pipeline

software for automatic analysis of bisulfite

sequencing data

• CpGMM builder [under re-design for free deployment]

Luu et al, Bioinformatcis, 2017

NaviSE: Superenhancer Navigator doing

epigenomics signal algebra

Ascensión et al, BMC Bioinformatics 2017

Pluripotent

Multipotent

Unipotent

From basics to disease research

Fibroblast

NSC

iPSC

Neuron

Reprogramming

Differentiation Aging Moore et al., 2015, Science

Kim et al., 2015, EMBO

Erlich et al., 2015 Stem Cell Reports

Luu et al., 2013, Genome Research

Hargus et al., 2014, Cell Reports

Han et al., 2012, Cell Stem Cell

Kim et al., 2014, Nature Protocols

Hallmann, Araúzo et al, 2016, Stem Cell Res. Kim et al., 2008, Nature

Kim et al., 2009, Cell

Kim et al., 2009, Nature

Kim et al., 2009, Nature Protocols

The reprogramming triangle

A mechanism for the segregation of age in

mammalian neural stem cells

Moore et al., 2015, Science

NSC

NSC NSC

Differentiated NSC Differentiated NSC

NSC

Young

asymmetric division Old

asymmetric division

Good quality protein

Bad quality protein (marked with

ubiquitin)

NSC

Disregulation of

Lamin/Lmna between NSC

from young and old mices

Big data omics disclose molecular mechanisms of diseases

• Cancer – Urothelial carcinogenesis: Erichsen et al, 2018, Scientific Reports.

– Colon cancer metastasis: Marquez et al, 2018, International Journal of Cancer.

– Glioma: Torres-Bayona et al, 2018, Scientific Reports.

– Stromal cells in oncogenetic transformation: Rodriguez et al, 2014, Stem Cell Reports.

– Gastric cancer progression: Santos et al, 2016, Cancer Research.

– Cancer stem cells: Díaz-Carballo et al, 2014, DNA and Cell Biology .

• Neurodegenerative diseases – Fronto-temporal dementia: Erlich et al, 2015, Stem Cell Reports.

• Infectious diseases – Epigenomics-transcriptomics of malaria

Integration of transcriptomics and epigenomics data in malaria Malaria protective vaccination accelerates liver extramedullary erythropoiesis • Quraishy et al, Malaria Journal 2018.

• Quraishy et al, Parasitology Research 2017.

• Quraishy et al, Parasitology Research 2016.

• Dkhil et al, Journal of Steroid Biochemistry and Molecular Biology 2015.

• Quraishy et al, Parasitology Research 2014.

(Unpublished data)

The power of big data to answer biological questions

Metabolic engineering

Metabolic flux analysis (MFA)

Araúzo-Bravo and Kazuyuki, Journal of Biotechnology, 2003

Zaid et al, FEMS Microbiology Letters, 2004

Zaid et al, Applied Microbiology and Biotecnology. Letters, 2004

Peng et al, FEMS Microbiology Letters, 2004

Sarkar et al, Archives. of Microbiology, 2008

Araúzo-Bravo et al, Journal American Chemical Society, 2005

Ahmad et al, NAR, 2006

Araúzo-Bravo et al, NAR, 2008

Structural biology

DNA interactions with proteins

and drugs.

Protein communications

Data analytics of the injury to kidney repair in patients with chronic kidney disease (CKD)

Maria Villar Abel Gonzalez Frederic Deschaseaux

Data from

Colombia

France

Urko Aguirre Antonio Gimeno Yolanda García

Bases de datos administrativas

Historia Electrónica del paciente

País Vasco

variables clínicas paciente Modelización

predictiva

variables clínicas paciente Validación

externa

Bases de datos administrativas

Historia Electrónica del paciente Aragón

Figura 1: Proceso del desarrollo de la innovación Desarrollo

software/integración en el

sistema de información

Data from

País Vasco

Aragón

Alarm system of detection of adverse events in hyperglycaemia patients based on predictive

modeling

Data-Driven Drug Discovery for Wound Healing (4D-HEALING)

3 year EU project, 1.477.000 Euros, members from Spain, Germany, Slovenia, Slovakia, Austria, the United Kingdom.

4D-HEALING will map the four spatiotemporal dimensions of human wound healing: the transcriptome of thousands of cells from an in vivo monitored human wound will be analysed by RNAseq at single cell level.

Message to take home

• Important to share data: Free omics data allows discover biology research errors

• Important to develop data processing tools

• Big data omics disclose molecular mechanisms of diseases

• Big data clinics uncover unknown triggers of diseases

Acknowledgments

Computational Biology & Systems Biomedicine

Daniela Gerovska

Alex Martinez Ascensión

Mikel Arrospide Elgarresta

Javier Cabau Laporta

Olga Ibañez Sole

Leyre Ahedo Fontaneda

Hariz Irizar

Sugoi Retegi Carrión

Molecular Biomedicine

Ali Sharifi Zarchi

Arnoldo Muller Molina

Luu Phuc Loi

Hans R Scholer