The complexity of the model systems sharply increases along the drug discovery process, while only a limited number of experimental models are available that accurately reflect human disease.
Conventional in vitro and in vivo models cannot capture disease behavior in real patients, and tools – like CRISPR – don’t act like actual drugs. Drug discovery is costly, time consuming, model systems have poor translation rates to patients and do not significantly reduce the risk of failure in the clinic. This makes it incredibly hard to translate preclinical hypotheses to the clinic and create targeted drugs that truly help.
Before running any wet lab experiments, Turbine computationally simulates tumor cell behavior in patients to understand the complex mechanisms driving the disease. Simulations can reveal the right modality and combination approach to treat even the most resistant cancers. Observing these in silico experiments our biologists and translational experts gain insight into the molecular context by which mono- and combination therapies can potentially lead to patient benefit.
Guiding the R&D process with simulations can increase the chance of success in the clinic.
https://pubmed.ncbi.nlm.nih.gov/14518029/
https://www.nature.com/articles/s41467-021-25175-5
globaldata.com
We use the same “wiring diagram” for all 1600+ in vitro and in vivo models, with patient modeling currently under development.
Our bioplatform allows the setup of cells with distinct OMICS profiles. Behavior training for the models is a special case of Recurrent Neural Networks, using Tensorflow.
Models prepared for simulations are trained on 500.000+ data points (CRISPR, drug sensitivity viability and post-treatment RNASeq assays).
We finish model setup by creating copies with different biomarkers to pinpoint the ideal responders for the specific perturbations.
We can specify extrinsic molecular alterations, to generate a high number of models representative of patients, but non-existent in vitro.
We can introduce interventions at scale, using a versatile toolkit of dose dependent inhibition, interaction level perturbation or combination screens.
Simulating perturbations of models, biomarkers and (even) combinational therapies we generate a complex molecular readout of dose responses and IC50 values.
Filtering and evaluating simulation results enables us to reveal hidden mechanisms behind patient-specific response and its driving effects.
Unique insights on mechanism and the associated biomarkers enable an optimized process of state-of-the-art experimental validation.
Average pathway activity in sensitive and control cells is calculated with a proprietary, footprint-based method based on RNA-sequencing.
We use the same “wiring diagram” for all 1600+ in vitro and in vivo models, with patient modeling currently under development.
Our bioplatform allows the setup of cells with distinct OMICS profiles. Behavior training for the models is a special case of Recurrent Neural Networks, using Tensorflow.
Models prepared for simulations are trained on 500.000+ data points (CRISPR, drug sensitivity viability and post-treatment RNASeq assays).
We finish model setup by creating copies with different biomarkers to pinpoint the ideal responders for the specific perturbations.
We can specify extrinsic molecular alterations, to generate a high number of models representative of patients, but non-existent in vitro.
We can introduce interventions at scale, using a versatile toolkit of dose dependent inhibition, interaction level perturbation or combination screens.
Simulating perturbations of models, biomarkers and (even) combinational therapies we generate a complex molecular readout of dose responses and IC50 values.
Filtering and evaluating simulation results enables us to reveal hidden mechanisms behind patient-specific response and its driving effects.
Unique insights on mechanism and the associated biomarkers enable an optimized process of state-of-the-art experimental validation.
Average pathway activity in sensitive and control cells is calculated with a proprietary, footprint-based method based on RNA-sequencing.
Pioneering an approach that combines simulation with machine learning, we map and model how thousands of signaling proteins interact characterizing cellular level cancer behavior and response or resistance to treatment.
Our platform enables the simulation of drug-like effects from compounds that may not exist yet, on cells potentially unavailable for lab-based testing, like those of high unmet need cancer patients.
This approach will potentially allow us to predict not only what works in cells, mice and people but more importantly, why and how. Continuous iterations of simulations and proprietary in vitro and in vivo experiments confirm predictions and progress our pipeline while simultaneously improving the underlying Simulated Cell™.
As all programs and partnerships run on the latest version of the in silico cell model, training benefits accumulate, leading to a constantly improving platform. Using results to both generate the initial idea and to guide its iterations, as the models improve, this leads to a more rational process to undestand the underlying disease biology.
Our benchmarks show that simulations prevent 2 out of 3 failed experiments in vitro and every 2nd failure in vivo as well.
Case studies
Simulated Cells™ can be used to run the equivalent of any preclinical or clinical protocol, at computational speed and scale. Running millions of simulations before conducting the most promising wet experiments, Turbine’s platform guides every step from target ID to clinical Proof of Concept.
Simulating cancer behavior to understand drivers of disease & mechanisms of resistance observed in clinical settings
Uncovering ideal patient population and combination strategy for therapies already in development or on the market
Identifying truly novel targets to manage unmet need in patients who don’t benefit from existing therapies
Building an engineer’s toolkit to understand biology requires software and data scientists who wish to enable biological translational science instead of replacing it.
Our team combines the amazing molecular biology, network- and data science expertise in Hungary with seasoned drug developers from the UK and the US. We’re here to change the status quo and bring truly impactful, simulation-guided therapies to patients.
“Working here has been quite a journey since day one. Not only the substantial progress we’ve achieved so far, but also personally: as a biologist, I was lured into the field of data analysis. We also have the most inspiring community, with talented and ‘crazy’ people. I’m really a Turbine-addict.”
“Turbine is one of those rare places where a software engineer can have literally lifesaving impact. We work closely with the researchers and witness every day how they use our platform to get better and better predictions. The tech stack is cutting edge: cloud, AI, big data aren’t just buzzwords but practical tools we need to use. And as an added bonus, we get to learn about biology, medicine, and how scientific research works organically – just by being exposed to it constantly!”
“Turbine is an amazing community from various fields and backgrounds, working on the verge of current human knowledge, breaking barriers to succeed where no one else has even attempted to. We do this with relentless curiosity, healthy scepticism, knowing our strength is in our differences, and this inspires me day by day.”
Szabi used to consult for The Medical Futurist and is the former Head of Marketing for Tresorit, a leading, global, secure cloud technology startup. With his understanding of molecular biology, oncology and AI, he translates simulated biology into real world impact by pinpointing the most challenging aspects of the current drug development workflow. Today, he is responsible for building a team dedicated both to sound science and delivering results, and for turning Turbine’s disruptive technology into a ground-breaking business.
As a medical doctor specializing in cancer research at some of the world’s top research institutes, Daniel helps design innovative and durable treatments against cancer by converting our platform’s computational results into clinical interpretations. His main responsibility lies in understanding scientific and medical challenges, to then guide our team of biologists, translational and data scientists in generating novel findings to move better treatments to patients.
A computer scientist turned biochemist, Kristóf’s dream is to turn biology into an engineering discipline, enabling science to create human organs as efficiently as we make cars. Named one of the 35 Innovators under 35 in 2018 by MIT Tech Review Europe, Kristóf invented Turbine’s method of simulating human cells and is leading the R&D teams working on the Simulated Cell to make more and more hidden biology available to our internal and external projects.
