NETWORK BIOLOGY AND COMPLEX DISEASES Ahto Salumets
CENTRAL DOGMA OF BIOLOGY https://en.wikipedia.org/wiki/central_dogma_of_molecular_biology
http://www.qaraqalpaq.com/genetics.html CHROMOSOMES
SINGLE-NUCLEOTIDE POLYMORPHISM http://knowgenetics.org/snps/ http://cisncancer.org/research/what_we_know/biology/genetic_variation.html
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
What is a disease? COMPLEX DISEASES
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
What is a complex disease? COMPLEX DISEASES
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
How to study complex diseases? 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
HU, J.X. ET AL. NETWORK BIOLOGY CONCEPTS IN COMPLEX DISEASE COMORBIDITIES. NAT. REV. GENET. 17 (10), 615-629 (2016). NETWORK BIOLOGY
MULTIMORBIDITY SPACE HU, J.X. ET AL. NETWORK BIOLOGY CONCEPTS IN COMPLEX DISEASE COMORBIDITIES. NAT. REV. GENET. 17 (10), 615-629 (2016). 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
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
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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.com by 4 th of November 10:00 (PDF please)