CADI™ Discovery - description
The Mechanisms-Based Medicine Concept:
Understanding and validating the mechanisms of a disease/disorder becomes the first objective. Finding the most adapted solutions is a necessary consequence of the first objective
- DISEASE/DISORDER: Describe the physiopathology of the disease/disorder with clinicians and patients feedback.
- MECHANISMS: Discover the causal versus symptomatic mechanisms of the disease/disorder.
- BIOMARKERS: Indirectly based on causal mechanisms, identify relevant biomarkers or specific combination, signatures of biomarkers (biological, imagery, physical signals, etc…) that could measure defined mechanistic deregulations at different stages of the disease/disorder.
- TARGETS: based on the causal mechanisms, identify what could be the best targets (not only one) to specifically address the causative deregulations.
- SOLUTIONS: We harness the mechanisms. Propose the most practical solutions to address the relevant mechanistic deregulations. It is important to notice that the proposed solutions, integrating diagnostics, therapies & patients follow-up, can be combinations of existing drugs, nutriments, devices, e-health, disease prevention tools and services, etc …
- FEED BACK LOOP: Integrate the results from e-R&D or e-Health experimentations into the validation process to improve global patient and disease/disorder follow-up.
The Life science modeling dilemma
- The mechanisms of life are complex, non-linear and integrative.
- In “living complex” systems, the functions of biological components and mechanisms are event and context-dependent. Classical “Cartesian” modeling concepts & approaches, valid for the majority of man-made artifacts, imply the concept of a “blue-print”. But this concept is at the opposite of biological reality.
- While “Cartesian” Bioinformatics and Mathematical tools have proven to be efficient to collect, structure, analyze, simulate specific functions to test or generate innovative hypotheses, yet…
- The “garbage in, garbage out” reality, tells us that the information produced and published (even in leading scientific journals) is necessarily ALWAYS incomplete, biased and erroneous to unknown extents.
- Big Data, due to life sciences reality, generally means “Big Garbage”.
- High value Smart Data, necessarily needs to be contextualized, with patients base-lines, and related to biological mechanisms.
- Statistics, serendipity or massive big data cannot be the “only” medical research options to deciphering the mechanisms of complex diseases.
- Despite increasing investments in Technology & I.T., major drugs products submissions to FDA are constantly declining.
CADI™ Discovery platform a proven operational answer, to implement Mechanisms-Based Medicine,
- A heuristic multi-systems multi-scale systems biology approach to addresses complex, non-linear and integrative issues.
- A revised discovery and validation process to address complex diseases issues using necessary mechanisms understanding.
- A novel continuum between e-R&D and e-Health to enlarge and strengthen the translational medicine paradigm and extract the maximum pertinent value from scientific, medical & health data.
- A proactive search of cost-effective solutions with lower short term failure risks exploiting the growing number of well documented off-patent molecules, multiple devices and e-health tools, disease prevention tools and services.
- The discovery of new drugs is possible.
- A systematic search of synergies between our research domains to optimize our proprietary CADI™ Knowledge database value through cost-effective novel applications
CADI™ Modeling : The first “heuristic” modeling approach, successfully applying its 5 principles
- “Architectural Principles” Approach;
- “Negative Selection” Process;
- “4 steps validation” Process;
- Broad life sciences & IT Expertise;
- “Synergic collaboration” with classical IT partners.
The second generation tools, CADI™ Process, development started in 2002
The unique CADI™ 4 steps validation process
The CADI™ 4 steps validation process starts when the integrative biology researchers generate the initial CADI™ model
The initial CADI™ Ver.0 model is constructed by "integrative biology" researchers.
- Step 1: For each loop, "integrative biology" researchers integrate the experimental results to generate the next CADI™ Ver. n+1 model .
- Step 2: CADI™ model forecasts are defined by both experimental and integrative biology researchers The "experimental biology" researchers define and/or invent new innovative experimentations to test the models forecasts.
- Step 3: "Experimental biology" researchers implement the innovative experimental approaches to test the model forecasts.
- Step 4: Experimental results are analyzed and interpreted by both experimental and integrative biology researchers.
The CADI™ 4 steps validation process stops when no key unexpected results are reported.
The first generation (abandoned in 2001): Bio-Graph™ (1998-2001)
- This initial "Cartesian" integrative plate-form, called "Bio-Graph™" because largely based upon graph theories, was developed over the period 1998-2001
- This technology allowed the production of the first biological models of complex human pathologies ever produced (Tamoxifen resistance, partly with the CADI™ prototype)
- However, this approach was extremely limited on several fronts:
- It required that all the papers be annotated before use, etc...
- It required massive amounts of human intervention at all stages of the analytical process and,
- while allowing to efficiently analyze at the cellular level, it was woefully inadequate for tasks where different tissues or organs had to be taken into consideration.