Mechanistic models approach to the assessment of inter patient heterogeneity.

The great advance in genomic sequencing technologies has provoked a great development in the
study of existing RNA in cell, tissue or organ. Consequently, various publications have shown how
the study of signaling circuits, inferred from gene activity, can help us understand aspects of cell
functionality, one of the great challenges for precision medicine.

We propose the use of a mechanistic model, which calculates the intensity of signal transmission
along signaling pathways based on transcriptomic data from different patients. Besides, thanks to
projects such as The Genotype-Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA),
where more than 30 additional healthy and different types of tumor samples are collected and
characterized respectively, transcriptomic data-sets have been created. Therefore, we could use
these transcriptomic data to study the heterogeneity between inter patients.

In the first place, in order to develop our study, we used gene expression data from GTEx and
calculated the activity of KEGG pathways using Hipathia for each tissue available. This way, we
know which intensities of signal transmission along signaling pathways are characteristic of every
tissue. Subsequently, pathways activities have been related with different factors such as sex and
age and their effects in the pathway activity have been studied. On the other hand, we used
transcriptomic data set from TCGA and Hipathia to calculate the activity of KEGG pathways for
each type of collected tumor. These results allow us to know which circuits changed according to
every person with a common disease. Plus, we find out which signaling circuits have a relevant role
in the development of a specific type of cancer.

Finally, we conclude that the use of mechanistic models together with the transcriptomic data of the
projects mentioned here would provide us crucial information to achieve the greatest challenge of
precision medicine.