An example on how to explore MK4MDD

Currently, the molecular mechanism of MDD, especially how effect proteins play roles in MDD, is still unclear. To further investigate this, we can navigate the database following these steps:

1) By using ‘Cross Data Search’ (Figure 1), we search relationships between ‘protein’ (Component A) and ‘neurobiological system, brain morphology and function, cognition and behavior, symptoms and signs’ (Component B). There are a total of 144 results.

Figure 1 Cross data search and search result.

2) We added search results into ‘My Relationship Set’ for dynamic visualization of components and relationships (Figure 2) and there are total of 132 non-repeated relationships. Based on the data network, we can see many experimental proofs for several biological hypotheses of the pathophysiology of MDD [1], one of them is the brain-derived neurotrophic factor (BDNF) as a proof for hypothesis of impairment of neurotrophic mechanism [2]. So we selected BDNF for further study.

Figure 2 My relationship set generated from cross search result.

3) To get a systematic overview about research status of BDNF protein, we click the ball to enter the ‘Component Report’. By ‘Protein Report’ for BDNF, we got 17 components related with BDNF protein, as well as relationship between BDNF protein and BDNF gene from supplementary annotation (Figure 3). By ‘Gene Report’ for BDNF gene, we acquired 13 components related with BDNF gene.

Figure 3 BDNF protein and BDNF gene component report.

4) To improve the focus of investigation, we deleted the previous 132 relationships from the broad range of searches and added all the 30 relationships surrounding both BDNF protein and BDNF gene into ‘My Relationship Set'. Finally the reiterative analytical process resulted in 31 relationships (including the relationship between BDNF protein and BDNF gene) in my relationship set (Figure 4).

Figure 4 Data network surrounding BDNF protein and BDNF gene.

From the graphical presentation of components and relationships, we find that BDNF protein is connected with protein CERB (cyclic AMP-responsive element-binding protein 1); gene BDNF is also connected with protein CERB and brain region amygdala. Based on this information, we may propose several hypotheses which have not been reported before. For example, would BDNF contribute to MDD by regulating CREB in amgdala? What cognitive impairments are caused by molecular activation mentioned above? Dose BDNF related symptoms (depression mood, anhedonia and suicide) appear based on this potential mechanism? New hypotheses will help drive new findings to further our knowledge on MDD mechanism.

1. Belmaker RH, Agam G. Major depressive disorder. N Engl J Med 2008; 358(1): 55-68.
2. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002; 34(1): 13-25.