NETWORK BIOLOGY AND COMPLEX DISEASESAhto Salumets

CENTRAL DOGMA OF BIOLOGY

https://en.wikipedia.org/wiki/Central_dogma_of_molecular_biology

CHROMOSOMES

http://www.qaraqalpaq.com/genetics.html

SINGLE-NUCLEOTIDEPOLYMORPHISM

http://cisncancer.org/research/what_we_know/biology/genetic_variation.htmlhttp://knowgenetics.org/snps/

• SNP-s may fall within coding sequences of genes, non-coding regions of genes or in the regions between the genes

• Some SNP-s may change how effectively gene is transcribed or change the structure and function of a protein

• SNP-s underlie differences in our susceptibility to disease

COMPLEX DISEASES

•What is a disease?

COMPLEX DISEASES

•What is a disease?• A disease is an abnormal condition that affects part or all of an

organism and it is associated with specific symptoms

COMPLEX DISEASES

•What is a complex disease?

COMPLEX DISEASES

• Nearly all diseases have a genetic component• There are over 4000 human diseases which are caused by single-gene

defect

http://kidshealth.org/en/parents/sickle-cell-anemia.html

COMPLEX DISEASES

• complex diseases are caused by a combination of genetic, environmental, and lifestyle factors

COMPLEX DISEASES

• A single SNP may cause a Mendelian disease, though for complex diseases, SNPs do not usually function individually, rather, they work in coordination with other SNPs to manifest a disease condition as has been seen in osteoporosis

http://qpilates.net.au/osteoporosis-and-pilates/

COMPLEX DISEASES

• Caused by multiple genes in combination with lifestyle and environmental factors

• Tend to co-occur with other complex diseases• Tend to progress in time• Hard to study and treat• The most frequent diseases are complex diseases

COMPLEX DISEASES

• How to study complex diseases?

NETWORK BIOLOGY

• Network biology enables us to model underlying mechanisms of diseases• e.g. we can study those diseases at a level of genes and proteins

NETWORK BIOLOGY

HU, J.X. ET AL. NETWORK BIOLOGY CONCEPTS IN COMPLEX DISEASE COMORBIDITIES. NAT. REV. GENET. 17 (10), 615-629 (2016).

MULTIMORBIDITY SPACE

• An individual’s disease state can be represented as a point in a multimorbidity space, where the axes represent quantitative measures of

different diseases. The grey axes represent the fact that the multimorbidity space is not limited to only three disease dimensions but can

instead span numerous dimensions. A patient’s temporal disease trajectory can be described as transitions (represented by dashed arrows)

between points in this space. These transitions will be facilitated by the effects of genetic and environmental parameters (red arrow).

HU, J.X. ET AL. NETWORK BIOLOGY CONCEPTS IN COMPLEX DISEASE COMORBIDITIES. NAT. REV. GENET. 17 (10), 615-629 (2016).

COMPLEX DISEASES + NETWORK BIOLOGY

HU, J.X. ET AL. NETWORK BIOLOGY CONCEPTS IN COMPLEX DISEASE COMORBIDITIES. NAT. REV. GENET. 17 (10), 615-629 (2016).

IMPORTANCE

• Personalized medicine programs are currently being initiated all over the world

• Ample of electronic health data and molecular-level data for millions of individuals are generated

• The molecular-level data often reflect dynamic changes • Opportunities for producing dynamic models at the level of molecular

network biology • Possibilities for understanding the molecular underpinning of diseases (and

co-occurrences) and applying best treatment

CONCLUSION

• Complex diseases are caused by a combination of genetic, environmental, and lifestyle factors, they tend to co-occur with other diseases and hard to study and treat

• Advances in technology enables to generate and collect a lot of data • Based on that data it is possible to generate biological networks• Those biological networks allow us to examine biological mechanisms

behind complex diseases and help us to find best treatments

THANK YOU FOR LISTENING!

HOMEWORK

• Describe a complex disease, give some examples of common complex diseases

• What is a node degree (k)? (little hint: networks consist of nodes and edges that connect them. In biology, nodes can be, for example, proteins and edges can be physical relationships between them)

• Are biological networks usually random networks or scale-free networks? Why?

• Find some projects which are associated with biological networks and describe their goal in a couple of sentences

Please send homeworks to ahtosalumets@gmail.comby 4th of November 10:00

(PDF please)