AI Reveals Previously Unknown Biology – We Might Not Know Half of What’s in Our Cells

Multi Scale Integrated Cell

UC San Diego researchers introduce Multi-Scale Integrated Cell (MuSIC), a technique that combines microscopy, biochemistry and artificial intelligence, revealing previously unknown cell components that may provide new clues to human development and disease. (Artist’s conceptual rendering.) Credit: UC San Diego Health Sciences

Artificial intelligence-based technique reveals previously unknown cell components that may provide new clues to human development and disease.

Most human diseases can be traced to malfunctioning parts of a cell — a tumor is able to grow because a gene wasn’t accurately translated into a particular protein or a metabolic disease arises because mitochondria aren’t firing properly, for example. But to understand what parts of a cell can go wrong in a disease, scientists first need to have a complete list of parts.

By combining microscopy, biochemistry techniques and artificial intelligence, researchers at University of California San Diego School of Medicine and collaborators have taken what they think may turn out to be a significant leap forward in the understanding of human cells.

The technique, known as Multi-Scale Integrated Cell (MuSIC), is described on November 24, 2021, in Nature.

“If you imagine a cell, you probably picture the colorful diagram in your cell biology textbook, with mitochondria, endoplasmic reticulum and nucleus. But is that the whole story? Definitely not,” said Trey Ideker, PhD, professor at UC San Diego School of Medicine and Moores Cancer Center. “Scientists have long realized there’s more that we don’t know than we know, but now we finally have a way to look deeper.”

Ideker led the study with Emma Lundberg, PhD, of KTH Royal Institute of Technology in Stockholm, Sweden and Stanford University.

Classic Cell vs MuSIC

Left: Classic textbook cell diagrams imply all parts are clearly visible and defined. (Credit: OpenStax/Wikimedia). Right: A new cell map generated by MuSIC technic reveals many novel components. Gold nodes represent known cell components, purple nodes represent new components. The size of node reflects number of distinct proteins in that component. Credit: UC San Diego Health Sciences

In the pilot study, MuSIC revealed approximately 70 components contained within a human kidney cell line, half of which had never been seen before. In one example, the researchers spotted a group of proteins forming an unfamiliar structure. Working with UC San Diego colleague Gene Yeo, PhD, they eventually determined the structure to be a new complex of proteins that binds RNA. The complex is likely involved in splicing, an important cellular event that enables the translation of genes to proteins, and helps determine which genes are activated at which times.

The insides of cells — and the many proteins found there — are typically studied using one of two techniques: microscope imaging or biophysical association. With imaging, researchers add florescent tags of various colors to proteins of interest and track their movements and associations across the microscope’s field of view. To look at biophysical associations, researchers might use an antibody specific to a protein to pull it out of the cell and see what else is attached to it.

The team has been interested in mapping the inner workings of cells for many years. What’s different about MuSIC is the use of deep learning to map the cell directly from cellular microscopy images.

“The combination of these technologies is unique and powerful because it’s the first time measurements at vastly different scales have been brought together,” said study first author Yue Qin, a Bioinformatics and Systems Biology graduate student in Ideker’s lab.

Microscopes allow scientists to see down to the level of a single micron, about the size of some organelles, such as mitochondria. Smaller elements, such as individual proteins and protein complexes, can’t be seen through a microscope. Biochemistry techniques, which start with a single protein, allow scientists to get down to the nanometer scale. (A nanometer is one-billionth of a meter, or 1,000 microns.)

“But how do you bridge that gap from nanometer to micron scale? That has long been a big hurdle in the biological sciences,” said Ideker, who is also founder of the UC Cancer Cell Map Initiative and the UC San Diego Center for Computational Biology and Bioinformatics. “Turns out you can do it with artificial intelligence — looking at data from multiple sources and asking the system to assemble it into a model of a cell.”

The team trained the MuSIC artificial intelligence platform to look at all the data and construct a model of the cell. The system doesn’t yet map the cell contents to specific locations, like a textbook diagram, in part because their locations aren’t necessarily fixed. Instead, component locations are fluid and change depending on cell type and situation.

Ideker noted this was a pilot study to test MuSIC. They’ve only looked at 661 proteins and one cell type.

“The clear next step is to blow through the entire human cell,” Ideker said, “and then move to different cell types, people and species. Eventually, we might be able to better understand the molecular basis of many diseases by comparing what’s different between healthy and diseased cells.”

Reference: “A multi-scale map of cell structure fusing protein images and interactions” by Yue Qin, Edward L. Huttlin, Casper F. Winsnes, Maya L. Gosztyla, Ludivine Wacheul, Marcus R. Kelly, Steven M. Blue, Fan Zheng, Michael Chen, Leah V. Schaffer, Katherine Licon, Anna Bäckström, Laura Pontano Vaites, John J. Lee, Wei Ouyang, Sophie N. Liu, Tian Zhang, Erica Silva, Jisoo Park, Adriana Pitea, Jason F. Kreisberg, Steven P. Gygi, Jianzhu Ma, J. Wade Harper, Gene W. Yeo, Denis L. J. Lafontaine, Emma Lundberg and Trey Ideker, 24 November 2021, Nature.
DOI: 10.1038/s41586-021-04115-9

Co-authors include: Maya L. Gosztyla, Marcus R. Kelly, Steven M. Blue, Fan Zheng, Michael Chen, Leah V. Schaffer, Katherine Licon, John J. Lee, Sophie N. Liu, Erica Silva, Jisoo Park, Adriana Pitea, Jason F. Kreisberg, UC San Diego; Edward L. Huttlin, Laura Pontano Vaites, Tian Zhang, Steven P. Gygi, J. Wade Harper, Harvard Medical School; Casper F. Winsnes, Anna Bäckström, Wei Ouyang, KTH Royal Institute of Technology; Ludivine Wacheul, Denis L. J. Lafontaine, Université Libre de Bruxelles; and Jianzhu Ma, Peking University.

Funding for this research came, in part, from the National Institutes of Health (grants U54CA209891, U01MH115747, F99CA264422, P41GM103504, R01HG009979, U24HG006673, U41HG009889, R01HL137223, R01HG004659, R50CA243885), Google Ventures, Erling-Persson Family Foundation, Knut and Alice Wallenberg Foundation (grant 2016.0204), Swedish Research Council (grant 2017-05327), Belgian Fonds de la Recherche Scientifique, Université Libre de Bruxelles, European Joint Programme on Rare Diseases, Région Wallonne, Internationale Brachet Stiftung, and Epitran COST action (grant CA16120).

Disclosures: Trey Ideker is co-founder of, on the Scientific Advisory Board and has an equity interest in Data4Cure, Inc. Ideker is also on the Scientific Advisory Board, has an equity interest in and receives sponsored research funding from Ideaya BioSciences, Inc. Gene Yeo is a co-founder, member of the Board of Directors, on the Scientific Advisory Board, an equity holder and a paid consultant for Locanabio and Eclipse BioInnovations. Yeo is also a visiting professor at the National University of Singapore. The terms of these arrangements have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies. Emma Lundberg is on the Scientific Advisory Boards of and has equity interests in Cartography Biosciences, Nautilus Biotechnology and Interline Therapeutics. J. Wade Harper is a co-founder of, on the Scientific Advisory Board and has an equity interest in Caraway Therapeutics. Harper is also Founding Scientific Advisor for Interline Therapeutics.

2 Comments on "AI Reveals Previously Unknown Biology – We Might Not Know Half of What’s in Our Cells"

  1. Re: “(A nanometer is one-billionth of a meter, or 1,000 microns.)”

    You have that backwards. One micron is 1,000 nanometers.

  2. Babu G. Ranganathan | November 26, 2021 at 7:43 am | Reply

    Babu G. Ranganathan*
    (B.A. Bible/Biology)

    THE CELL could not have evolved. A partially evolved cell would quickly disintegrate under the effects of random forces of the environment, especially without the protection of a complete and fully functioning cell membrane. A partially evolved cell cannot wait millions of years for chance to make it complete and living! In fact, it couldn’t have even reached the partially evolved state.

    CATCH-22 FOR EVOLUTIONARY ORIGIN OF LIFE

    Just having the right materials, elements, and conditions do not mean that life can arise by chance.

    Miller, in his famous experiment in 1953 showed that individual amino acids (the building blocks of life) could come into existence by chance. But, it’s not enough just to have amino acids. The various amino acids that make-up life must link together in a precise sequence, just like the letters in a sentence, to form functioning protein molecules. If they’re not in the right sequence the protein molecules won’t work. It has never been shown that various amino acids can bind together into a sequence by chance to form protein molecules. Even the simplest cell is made up of many millions of various protein molecules.

    What many don’t realize is that although oxygen is necessary for life’s processes, the presence of oxygen would prevent life from coming into being. This is because oxygen is destructive unless there are mechanisms already in place to control, direct, and regulate it, such as what we find in already existing forms of life.

    RNA and DNA are made up of molecules (nucleic acids) that must also exist in the right sequence. Furthermore, none of these sequential molecules, proteins, DNA, RNA, can function outside of a complete and living cell and all are mutually dependent on one another. One cannot come into existence without the other.

    Mathematicians have said any event in the universe with odds of 10 to 50th power or greater is impossible! The probability of just a single average size protein molecule arising by chance is 10 to the 65th power. The late great British scientist Sir Frederick Hoyle calculated that the odds of even the simplest cell coming into existence by chance is 10 to the 40,000th power! How large is this? Consider that the total number of atoms in our universe is 10 to the 82nd power.

    The cell could not have evolved. A partially evolved cell would quickly disintegrate under the effects of random forces of the environment, especially without the protection of a complete and fully functioning cell membrane. A partially evolved cell cannot wait millions of years for chance to make it complete and living! In fact, it couldn’t have even reached the partially evolved state.

    Alien beings, even if they do exist, could not have evolved. How could they have survived millions of years while the very biological structures, organs, and systems necessary for their survival were supposedly still evolving? Life, in any form (even a single-celled organism), must be complete, fully integrated, and fully-functioning from the very start to be fit for survival.

    Of course, once there is a complete and living cell then the code and mechanisms exist to direct the formation of more cells. The problem for evolutionists is how did the cell originate when there were no directing code and mechanisms in nature. Natural laws may explain how a cell or airplane works but mere undirected natural laws could not have brought about the existence of either.

    What about synthetic life? Scientists didn’t create life itself. What they’ve done is, by using intelligent design and sophisticated technology, scientists built DNA code from scratch and then they implanted that man-made DNA into an already existing living cell and alter that cell. That’s what synthetic life is.

    Through genetic engineering scientists have been able to produce new forms of life by altering already existing forms of life, but they have never created life from non-living matter. Even if they do, it won’t be by chance but by intelligent design. That doesn’t help the theory of evolution.

    What about natural selection? Natural selection doesn’t create or produce anything. It can only “select” from biological variations that are possible and which have survival value. If a variation occurs that helps a species survive, that survival is called ” natural selection.” It’s a passive process. There’s no conscious selection by nature, and natural selection only operates in nature once there is life and reproduction and not before, so it would not be of assistance to the origin of life.

    Science can’t prove we’re here by chance or design. Neither was observed. Both are positions of faith. The issue is which faith is best supported by science. Let the scientific arguments of both sides be presented.

    Read my popular Internet articles:

    THE NATURAL LIMITS TO EVOLUTION
    ANY LIFE ON MARS CAME FROM EARTH

    Visit my Internet site: THE SCIENCE SUPPORTING CREATION

    Author of the popular Internet article, TRADITIONAL DOCTRINE OF HELL EVOLVED FROM GREEK ROOTS

    *I have given successful lectures (with question and answer period afterwards) defending creation before evolutionist science faculty and students at various colleges and universities. I’ve been privileged to be recognized in the 24th edition of Marquis “Who’s Who in The East” for my writings on religion and science.

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