Want to know which mutations are really risky? New Scripps Research method may help Study bridges basic science and techniques to advance therapeutics.
August 28, 2018
We're all mutants, explains William Balch, PhD, a professor at Scripps Research. Scientists have long assumed that a person who appeared healthy had a relatively normal genome. But we're now realizing that variation is rampant and makes us who we are uniquely, he says.
That's why Balch and his lab have designed a way to look at a strand of DNA to find out what trait it codes for, or what deleterious mutation it might harbor. We need to understand how these variants contribute to a trait like the color of your hair or, importantly, the harmful ones, a disease, says Balch.
Until recently, there was no way to compare variants across large groups of people. Now, with the technology to sequence the human genome getting cheaper and cheaper, and with the launch of the national All of Us Research Program, Balch thinks we finally have enough data to determine how variants shape the population and each of us as individuals and how variants could inform drug design.
Balch and study first author Chao Wang, PhD, a postdoctoral associate at Scripps Research, describe their tool for studying human genomes in a paper out recently in the journal Cell Reports. Using a statistical method called Gaussian-process based machine learning, scientists can now take a gene, any gene, and using only a few of the many variants found in the population, discover the many shapes of the protein it encodes for and the many functions of those shapes.
This tells us how the entire protein is put together from a dynamic and biologically relevant perspective and what happens when there is a defect, Balch says.
As a proof of concept, the team looked at genetic variants in people with cystic fibrosis. The sparse collection of variants the researchers focused on sit on different spots on the DNA code. When this code is read by the cell to make a protein, the variants code for specific amino acids the building blocks of the protein.
Now, with their new variation spatial profiling' method that captures sequence meaning through its functions, the DNA code takes on a new physical structure a phenotype landscape, as Balch sees it, that can be mined.
On that landscape sit the data points of collected variants that tell something about the protein's many roles in the worldwide population. These data points are like boreholes delineated on a physical map that, when analyzed together, help the petroleum industry determine where to drill for oil. We've adapted that to biology, Balch says.
On the protein, these trusted variant locations told Wang and Balch where the protein was vulnerable to mutations that cause cystic fibrosis. Using a new biological principle, they termed spatial covariance,' by analogy to its use in physics, geology and machine learning, their analysis then predicted the likelihood where uncharacterized mutations found in the rest of the protein could also cause disease.
From a sparse amount of information, we can measure the consequences of variation across the entire protein, says Balch. A second test showed the method could also assess variants linked to Alzheimer's disease to predict onset. The approach is universal in design and can be applied to many challenging questions in understanding human disease, from neurodegeneration to cancer.
The new method could prove useful in assessing future therapies as Wang and Balch showed how spatial covariance can predict the response of variation in the population to a therapeutic. Many drugs fail in clinical testing because they only help a fraction of people and are developed with disease models with poor relevance to human biology. A better understanding of human genetic variation in the early stages of drug development may now reveal how different pathways in the population will respond to drug treatment, and how drugs can be tailored for personalized medicine.
We are using evolution's rules to understand you' by looking at how the rules are played out in all of us,' says Balch.
The work in this study is part of a growing effort to use machine learning to inform biology and medicine. For example, Oxford's Mihaela van der Schaar, PhD, is harnessing a different form of machine learning using clinical data directly to make recommendations for patient care. And Caltech's Francis Arnold, PhD, is pioneering use of Gaussian processing to engineer proteins for practical industrial processes.
Balch and Wang are now taking advantage of rapid advances in artificial intelligence to understand how variants interact across the entire genome to predict and manage human biology.
This is just step one as we recognize the approach will enable a deeper understanding of central dogma [DNA to RNA to protein] in a new spatial framework, its role in natural selection and perhaps our origins, Balch says.
The study, Bridging Genomics to Phenomics at Atomic Resolution through Variation Spatial Processing, was supported by the National Institutes of Health (grants HL095524, DK051870 and AG049665), the Tobacco-Related Disease Research Program (grant TRDRP 23RT-0012) and by Cystic Fibrosis Foundation Therapeutics.
Molecular and Cellular Biology Balch, William
Most recent headlines
09/11/2025
Dalet today announced a transformative leap forward for media operations: Agentic Artificial Intelligence (AI) that unifies the Dalet ecosystem under one natura...
23/10/2025
A deadline is looming for a new carriage deal between Verizon's Fios TV and Nexstar, with both Verizon and the pay TV-backed American Television Alliance bl...
23/10/2025
NEW YORK During a high-profile session at NAB Show New York, new survey data was shared that revealed significant public concern over artificial intelligence (A...
23/10/2025
BELLEVUE, Wash. and NEW YORK Fox Weather has tapped T-Mobile has as its preferred communications provider and announced that all Fox Weather reporters are being...
23/10/2025
PBS and Amazon Web Services have announced the network is using generative AI to provide enhanced search results to viewers on the PBS App and PBS LearningMedia...
22/10/2025
Prime Video Inks Deal To Present NFL Black Friday Game Worldwide By SVG Staff
Wednesday, October 22, 2025 - 10:06 am
Print This Story | Subscribe
Story ...
22/10/2025
NBA Tip-Off: ESPN Goes 1080p HDR End-to-End, Flipping HDR Switch on REMI and REM...
22/10/2025
FloSports Empowers Division II, III Athletic Departments With Turnkey Production...
22/10/2025
Wall Street Video Summit Debuts, Bringing Together 200 Financial Enterprise Vide...
22/10/2025
Dueling Pianos: International Chopin Piano Competition Is as Competitive as a Ba...
22/10/2025
In 1995, a young Colombian artist released an album that would change Latin pop ...
22/10/2025
Over the past few months, a photovoltaic system has been installed on a three-he...
22/10/2025
The Orion spacecraft for NASA's Artemis II mission is stacked on the Space Launch System (SLS) rocket in High Bay 3 of the Vehicle Assembly Building at Kenn...
22/10/2025
L3Harris' Hybrid SATCOM is resilient by design, offering path diversity that eliminates vulnerabilities by routing data across the best available networks i...
22/10/2025
WASHINGTON, D.C. Organizers of NAB Show New York said they are expecting more than 12,000 registered attendees from about 100 countries along with 260 exhibitor...
22/10/2025
WASHINGTON, D.C The organizers of The 2025 NAB Show New York have announced that they are expecting more than 12,000 registered attendees from about 100 countr...
22/10/2025
Masque Sound, a leading theatrical sound reinforcement, installation and design company, supplied an extensive gear package of professional-grade equipment for ...
22/10/2025
Lightware, a global leader in signal management and AV connectivity solutions, is seeing strong market momentum for the UCX-3x3-TPX-RX20, a compact transmitter-...
22/10/2025
MELVILLE, N.Y. Chyron has released PAINT 10.2, the latest update for its telestration platform, adding support for SMPTE ST 2110 IP workflows, expanding brandin...
22/10/2025
WASHINGTON Run3TV today said NBCUniversal is joining as an investor in the ATSC 3.0 Framework Authority, which develops the Run3TV NextGen TV application platfo...
22/10/2025
ATLANTA swXtch.io will feature two new networking solutions extending the company's reach across more cloud and on-prem workflows at NAB Show New York, set ...
22/10/2025
The Warner Bros. Discoverys HBO Max streaming services has increased prices for all its streaming tiers effectively immediately for new customers. Existing cust...
22/10/2025
LOS ANGELES OpenDrives has signed a new distribution partnership deal with Versatile Distribution Services (VDS) to strengthen its channel and streamline how it...
22/10/2025
WASHINGTON, D.C The organizers of The 2025 NAB Show New York have announced that they are expecting more than 12,000 registered attendees from about 100 countr...
22/10/2025
Samora Pinderhughes Brings Immersive Sound to Berklee's Signature Series The artist and composer, who's worked with Herbie Hancock, Robert Glasper, Co...
22/10/2025
BMI Day at Berklee Celebrates Composer Fil Eisler and Awards Scholarship to Stud...
22/10/2025
October 22nd, 2025 TRIBECA ANNOUNCES STAR-STUDDED LINEUP OF MEMBERSHIP EVENTS F...
22/10/2025
Rohde & Schwarz and TRUMPF cooperate in drone defense Rohde & Schwarz and TRUMPF partner to deliver a comprehensive drone defense solution combining Rohde & S...
22/10/2025
European Broadcaster Upgrades To Grass Valley's NativeIP LDX 135 Cameras And...
22/10/2025
Everyone Gets a Better Deal on Verizon with New FOX One Perk The $15 FOX One streaming service perk is yet another way Verizon continues to add savings for cu...
22/10/2025
First Look Hidden Assets Series 3
Premieres on 9th November 9:30pm on RT One & RT Player
WATCH HERE Promo Link: Hidden Assets Series 3 | RT
The Crimin...
21/10/2025
NAB New York 2025: Although AES Show Is on Its Own, Audio Will Be a Major Part o...
21/10/2025
NAB New York 2025: Business of Broadcast and Media,' Future of Content'...
21/10/2025
SVG All-Stars: Ethan Folz, Senior Director, Digital Operations and Quality of Ex...
21/10/2025
NBA on NBC/Peacock: Livestream Offers Graphic Overlays, Predictive Gaming, Ancil...
21/10/2025
NBA on NBC/Peacock: At the Front Bench With Producer Frank DiGraci and Director ...
21/10/2025
NBA on NBC/Peacock: NBC Sports, NEP Build Ultra-Flexible Production Plan That Se...
21/10/2025
Indigenous storytelling has been at the heart of the work of the Sundance Instit...
21/10/2025
Top L-R: Mysterious Skin, American Dream Second Row L-R: Little Miss Sunshine, D...
21/10/2025
Last week, Spotify and Columbia Records transformed Pier 4 at the Brooklyn Army ...
21/10/2025
SBS Learn's Dharug Ngurra resource empowers classrooms to meaningfully celeb...
21/10/2025
As global operators simplify and evolve their digital platforms, NPS improvement...
21/10/2025
Critical Design Review completion is a key milestone on the path toward Wideband Global Satellite Communications certification for the network in 2026, opening ...
21/10/2025
New Australian undersea training range to implement and improve warfighting tactics, proficiency and safety; enable joint/allied training that contributes to pr...
21/10/2025
eds3_5_jq(document).ready(function($) { $(#eds_sliderM519).chameleonSlider_2_1({...
21/10/2025
September, the beginning of autumn, brought an expected revival to the TV market, largely due to the new fall TV schedules. The time spent in front of the TV sc...
21/10/2025
Broadcast Booms with 20% Uptick vs. August, Achieving Largest Monthly
Increase ...
21/10/2025
During September, streaming's share of TV viewing in Mexico settled at 24.5%, a marginal shift of -0.5 share points from the previous month.
Disclaimer: YU...
21/10/2025
RENNES, France BBright and GlobalM have conducted a technical trial validating Ultra HD interoperability across the entire contribution chain in the cloud, achi...
Want to know which mutations are really risky? New Scripps Research method may help Study bridges basic science and techniques to advance therapeutics.
