Sachin Singh RawatSchool of Biotech, GGS IP University

A VISION FOR YOUR MOLECULAR HEALTH

Better measurementand visualization

Better mathematical tools to interpret data

Systems approachto biology

Systems medicine

P4 Medicine

Predictivemedicine

Preventivemedicine

Personalizedmedicine

Participatorymedicine

biology as an information science

Software generates the hardware !! Only portion of the program is executed in a

particular cell at a given time. How?? Two kinds of information characterize all central

mechanisms of life Digital information of the genome + environmental

signals Information handling structures: DNA, RNA Hierarchical levels of information: genes, proteins,

individual phenotype, gene pools, biome etc

systems approach to disease

The whole is more than the sum of its parts Whole - ∑ (parts) = emergent

properties Diseases are just network perturbations Dynamic alteration of expression of

information Interactome = Genome + Epigenome +

Transcriptome + Proteome + Metabolome + ….

reductionism holism (systems approach)

emerging technologies

Family genome sequencing Proteomics Metabolomics Single cell analysis Imaging Induced pluripotent stem cells

family genome sequencing In the next 10 years or so, individual genome

sequencing would be routine clinical practice 70% sequencing errors could be identified by using

plausability checks based on Mendelian genetics Rare variants would be identified immediately Accelerate search for disease-causing genes Actionable gene variants would allow specification of

how a patient can improve his health Get SNP’ed: know your pre-disposition to diseases

proteomics

20,000 human genes code for millions of proteins Comparing proteome across space and time

would enable new markers for diagnostics and drug design

Targeted proteomics: democratization of human proteins

Powerful tools in analyzing disease mechanisms, approaches to identification of biomarkers

metabolomics Using stable isotopes to follow the fate and rate of

individual metabolites, the measurement of metabolite fluxes

More information on disease progression and potential adaptive, compensatory physiological and patho-physiological mechanisms

MS-based methods to be complemented by pattern-recognition array-sensors to capture volatile metabolites in exhaled breath, providing disease-specific molecular signatures

E-noses: Non-invasive diagnostic devices

single cell analysis

Microfluidic technologies to study individual cells at the genomic and the proteomic levels

Number of discrete cell populations in a particular tissue or organ

Identification of cell surface molecules to categorize discrete populations

Characterization of disease states by cell surface molecules

imaging

Spatial and temporal information is critical for developing reliable disease models

Would allow identification of actionable network components

Need to develop advance high-resolution, high-content imaging

Would enable reliable interpretation of molecular processes in health and disease

Integrated into molecular diagnostics, medical decision support systems

induced pluripotent stem cells

First derived by Takahashi and Yamanaka (2006) Is a technique for cellular reprogramming Will be useful in exploring mechanisms of

disease initiation and progression Would reveal many secrets of development Will be crucial for curing antigen-specific

autoimmunity and allergies Accelerator for regenerative medicine Minimal immune response

the promise of p4 medicine

Will quantify wellness and demystify disease Each individual will be associated with a virtual

data cloud of billions of data points Data cloud will be reduced to simple

hypotheses on health and disease for each individual

Quantized self will provide real-time, readily-digestible insights into optimizing wellness

Stratification of diseases will revolutionize drug discovery

predictive medicine

Blood as a window into disease Molecular fingerprints of diseases Assessment of susceptibility to diseases based

on the genetic makeup (SNPs, ethnicity etc) HLA complex is associated with susceptibility

to >50 diseases Relative risk = % affected among those with allele % affected in the general population DR2 130X prone to nacrolepsy

preventive medicine

Designing therapeutic, preventive drugs via systems approaches

Systems approaches to create vaccines will transform prevention against infectious diseases

Reengineering of disease perturbed networks at the earliest

Shift from focus on disease to focus on wellness

personalized medicine

Different drugs for different genetic subsets of the population

Each person would be his/her own control Real-time monitoring of single cells to suggest

changes in the therapy being provided Need to safeguard against misuse by employers

or insurance companies

participatory medicine

Patient-driven social networks Cloud computing and crowd sourcing of medical

data Radical changes in medical school curricullum Big changes in the Big Pharma Emergence of new companies for development

and transfer of technologies involved Democratization of medicine Adequate healthcare affordable to all

systems approach to the prion disease

To identify DEGs, diseased brain transcriptomes were subtracted from control transcriptomes at 10 time points across disease progression.

7400 RNA transcripts, encoded by 1/3rd of mice genes were altered

4 major networks, involving 300 DEGs, appeared to participate in prion disease and the networks were altered sequentially

Dynamics of transcriptome alterations explained pathophysiology of disease

>100 brain-specific mouse transcripts could be identified, many of them encoding proteins secreted into blood

A brain-specific blood fingerprint that could distinguish for the brain –health from disease, and in case of disease, the type of disease– can be developed

“ ….In next 10-15 years, we will have a hand-held device which would measure around 50 proteins of each of the about 50 major organs

from just nanolitres of blood…. ”

reference

Hood, L., Balling, R., Auffray, C., Revolutionizing medicine in the 21st century through systems approaches, Biotechnol. J. 2012, 7, 992-1001

TED and other talks by Dr Leroy Hood

Thank you

Google Map of Human Metabolism