Breaking News
April 24, 2019 - Making Laboratories More Efficient with the Most Modern LIMS on the Market
April 24, 2019 - Treating cancer patients with personalized, combination therapies improves outcomes
April 24, 2019 - Researchers engineer new molecules to help stop lung cancer
April 24, 2019 - Acupuncture can be a wonderful tool for preventing number of diseases
April 24, 2019 - Daily life disability before hip replacement may predict poor post-operative outcomes
April 24, 2019 - Study finds involuntary staying in housing estates to be a potential health risk
April 24, 2019 - Older kidney disease patients starting dialysis die at higher rates than previously thought
April 24, 2019 - Time-restricted eating shows promise for controlling blood glucose levels
April 24, 2019 - Research provides important insight on the brain-body connection
April 24, 2019 - In 10 Years, Half Of Middle-Income Elders Won’t Be Able To Afford Housing, Medical Care
April 24, 2019 - Researchers study how E. coli clones have become major cause of drug-resistant infections
April 24, 2019 - Bacterial and fungal toxins found in popular electronic cigarettes
April 24, 2019 - Factors affecting absorption of ‘sunshine vitamin’ during spring/summer months
April 24, 2019 - Texting helps improve medication adherence, health outcomes for patients with schizophrenia
April 24, 2019 - Cochrane Review looks at different ways to use nicotine replacement therapies
April 24, 2019 - New review on relationship between COPD and Type 2 diabetes
April 24, 2019 - Brain areas linked to memory and emotion aid odor navigation in humans
April 24, 2019 - Brain stimulation reverses age-related memory loss
April 24, 2019 - Amid Opioid Prescriber Crackdown, Health Officials Reach Out To Pain Patients
April 24, 2019 - $4 million NIH award will help establish UCI Skin Biology Resource-based Center
April 24, 2019 - Cancer drugs reprogram genes in breast tumors to prevent endocrine resistance, finds study
April 24, 2019 - Combination-imaging technique provides new window into macaque brain connections
April 24, 2019 - Researchers identify new allergen responsible for allergy to durum wheat
April 24, 2019 - Researchers define role of rare, influential cells in the bone marrow
April 24, 2019 - DNA rearrangement may predict poor outcomes in multiple myeloma
April 24, 2019 - FDA Approves Skyrizi (risankizumab-rzaa) for Moderate to Severe Plaque Psoriasis
April 24, 2019 - Combination therapy might be beneficial in schizophrenia
April 24, 2019 - Blood test can help match cancer patients to early phase clinical trials
April 24, 2019 - Women tend to underreport snoring and underestimate its loudness
April 24, 2019 - Comprehensive molecular test introduced for diagnosis of malaria caused by P. vivax parasites
April 24, 2019 - New range prediction approach increases accuracy, safety and tolerability of proton therapy
April 24, 2019 - Need for Sedation Up for Regular Cannabis Users
April 24, 2019 - Lack of access to antibiotics is a major global health challenge
April 24, 2019 - New study provides better understanding on safety of deworming programs
April 24, 2019 - EEG used to detect impact of maternal stress on neurodevelopment in 2-month-old infants
April 24, 2019 - FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose
April 24, 2019 - A new way of finding compounds that prevent aging
April 24, 2019 - Mechanical training makes synthetic hydrogels perform more like muscle
April 24, 2019 - Study provides new insights into regulatory T cells’ role in protecting against autoimmune disease
April 24, 2019 - Pregnant women with type 1 diabetes are at greater risk of preterm birth
April 24, 2019 - ‘Tummy tuck’ can be safely performed in obese patients with no increase in complications
April 23, 2019 - ‘First’ 3-D print of heart with human tissue, vessels unveiled
April 23, 2019 - Which blood-based method works best to detect TB?
April 23, 2019 - Gene therapy cures infants suffering from ‘bubble boy’ immune disease
April 23, 2019 - Chemical-sampling wristbands detect similar exposures across three continents
April 23, 2019 - Management of Residual Limb Pain
April 23, 2019 - Molecular clock influences immune cell responses
April 23, 2019 - On the importance of culture, partnerships and diversity at the Dean’s Lecture Series
April 23, 2019 - Siddhartha Mukherjee Receives Lewis Thomas Prize for Writing About Science
April 23, 2019 - Dengue mosquito poses greatest danger of spreading Zika virus in Australia
April 23, 2019 - Scientists identify 104 high-risk genes for schizophrenia
April 23, 2019 - Abdominal etching can help patients to get classic ‘six-pack abs’ physique
April 23, 2019 - Alvogen Inc. Issues Voluntary Nationwide Recall of Fentanyl Transdermal System Due to Product Mislabeling
April 23, 2019 - Skype hypnotherapy is effective treatment for IBS
April 23, 2019 - The future hope of “flash” radiation cancer therapy
April 23, 2019 - Bicycling, Recycling, and Beyond: Public Safety to Host Shred Fest and Bike-to-Campus Day 
April 23, 2019 - Skipping breakfast linked with increased risk of death from heart disease
April 23, 2019 - Neuroscientists propose new theory about amyloid precursor protein connection in Alzheimer’s
April 23, 2019 - Mediterranean diet protects against overeating and obesity
April 23, 2019 - NUS scientists uncover novel biomarkers linked with ‘chemobrain’
April 23, 2019 - Novel ECCITE-seq technique expands multimodal single cell analysis
April 23, 2019 - Half of all American workplaces offer health and wellness programs
April 23, 2019 - Hypnosis may offer a genuine alternative to painkillers
April 23, 2019 - Sleep loss greatly interferes with job performance
April 23, 2019 - Study shows how elderberry fruit can help fight against influenza
April 23, 2019 - Parkinson’s sufferers regain mobility with new implant
April 23, 2019 - Perinatal Complications Tied to Childhood Social Anxiety
April 23, 2019 - Research reveals how immune cells help tumors escape body’s defenses
April 23, 2019 - UAB receives $17 million grant to explore immune cells in inaccessible tissues of the human body
April 23, 2019 - Opening blocked arteries may be lifesaver for older heart attack patients
April 23, 2019 - Yposkesi chairman to speak on ‘Manufacturing and the CDMO Perspective’ at Cell and Gene Meeting
April 23, 2019 - Listeria Outbreak Linked to Deli Meats, Cheeses in 4 States
April 23, 2019 - Scientists find another way HIV can hide from vaccines
April 23, 2019 - Improved WIC food packages reduced obesity risk for children, study finds
April 23, 2019 - EU ban on ‘meaty’ names for veggie food products would affect public sector
April 23, 2019 - KNAUER self-tests gender pay gap one month after Equal Pay Day
April 23, 2019 - Johns Hopkins study reports overdiagnosis of schizophrenia
April 23, 2019 - New approach to repair defects in fetal membranes could prevent life-long medical conditions
April 23, 2019 - Reviving the heart’s regenerative capacities using microRNAs
April 23, 2019 - New pediatric blood pressure guidelines can better predict kids at higher risk of heart disease
Modeling Non-Numerical Data in Systems Biology

Modeling Non-Numerical Data in Systems Biology

image_pdfDownload PDFimage_print

An interview with Dr. Eshan Mitra, Ph.D., from Los Alamos National Laboratory, discussing the importance of computer models in biology and the development of a more accurate model of the RAF phosphorylation pathway.

Why are computer models used in systems biology?

We use computer models to study processes in biology that are challenging to directly observe with experiments. Our models focus on cell signaling pathways: sets of proteins in a cell that work together to perform a certain function, such as cell growth.

By TampoImage Credit: Tampo / Shutterstock

We can use this type of model to understand and simulate how a cell would respond to a certain stimulus like a dose of a drug. We can understand how specific drugs operate at the level of individual cells, and also can consider new signaling proteins as potential drug targets.

How sophisticated are the current computer models used in drug development? Why is it important that new models are developed?

Current systems biology models try to describe how the concentrations of important signaling proteins in a cell change over time.

Typically the model can be written as a set of differential equations. These equations can be simulated on a computer to predict how a cell will respond to certain conditions, like a drug binding to a protein.

A challenge in building these models is choosing the associated numerical values, called model parameters. These could be quantities like the speed of a particular chemical reaction, or the concentration of an enzyme in the cell.

Often, these quantities are hard to measure directly. What we have to do instead is called parameter fitting: We look at some other protein in the model that was measured, and choose numerical values for the model so that the model output matches the experimental measurements.

Developing new and accurate models is important because it gives us predictive power. With an accurate model, we can look at a certain protein in the cell and ask, would this be a good drug target?If we blocked this protein’s activity, what would happen to the cell? But our predictions will only be as good as the model used to generate them.

By 123dartistImage Credit: 123dartist / Shutterstock

What is the RAF signaling pathway, and how is it involved in cancer?

RAF is a protein involved in a signaling pathway for cell growth. When a receptor at the surface of a cell receives a signal to grow, that signal passes through RAF on the way to telling the cell to grow.

In cancer, RAF can become mutated, such that it always tells the cell to grow, without a signal. This causes the uncontrolled growth of a tumor. Mutated RAF is found in about 60% of melanoma cases, and has also been seen in some cases of colon cancer and lung cancer.

As a result, RAF is a popular target for cancer drugs. If a drug blocked the activity of RAF, that could slow down the growth of a tumor. But targeting RAF has been challenging: many drug candidates designed to inhibit RAF have instead caused an increase in RAF activity.

In our paper, we analyzed a model of RAF that shows how these RAF-targeting drugs can go wrong.

Please describe the algorithm you recently developed.

When we analyze models like the model of RAF signaling, we want the numerical values in the model – reaction speeds and protein concentrations – to be as accurate as possible.

Typically what people do is find a “fit” for those values using numerical data. For example, you might have an experiment where someone measured the quantity of active RAF at different drug doses. Then you can tune the numerical values in the model so that the model agrees with the data.

What our approach does differently is it lets us also use non-numerical data to fit the model. For example, an experiment might show that a drug decreases RAF signaling, without specifying by how much.

By including this kind of measurement, we can put more information into our model, and that makes the model more accurate.

The exciting finding is that with enough of these non-numerical measurements, we can actually get numerical values for reaction speeds in the model, and use those to make numerical predictions.

Do you think that this approach should be applied to all drug interaction studies?

I am excited about the possible applications for this approach. Non-numerical experiments tend to be easier to perform than numerical ones, and as a result, most published cell biology experiments are non-numerical.

So if you’re building a new cell signaling model to find out how your new drug will work, there’s a good chance that there is already a published experiment that generated non-numerical data about what you’re looking at.

If so, then our approach makes it possible to include that information in the model. That makes for a more accurate model that is more likely to give you good predictions about the drug.

What are the next steps for your research?

I want to make this approach accessible to other researchers. My next step is developing an open-source computer program that runs the approach automatically.

The program reads in a cell signaling model, along with both numerical and non-numerical data, and runs an optimization algorithm to tune the model to agree with the data.

My hope is that this program will enable other biologists to apply our approach toward the next exciting medical discovery.

Where can readers find more information?

About Dr. Eshan Mitra

Dr. Eshan Mitra is a postdoctoral researcher at Los Alamos National Laboratory. Eshan earned his Ph.D. at Cornell University, where he studied the molecular mechanisms behind allergic responses.

His current work focuses on methods and software development for systems biology. Eshan is developing tools for simulating and analyzing models of cell signaling networks.

Tagged with:

About author

Related Articles