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Bow-tie signaling in c-di-GMP: Machine learning in a simple biochemical network.

Jinyuan Yan | Maxime Deforet | Kerry E Boyle | Rayees Rahman | Raymond Liang | Chinweike Okegbe | Lars E P Dietrich | Weigang Qiu | Joao B Xavier
PLoS computational biology | 2017

Bacteria of many species rely on a simple molecule, the intracellular secondary messenger c-di-GMP (Bis-(3'-5')-cyclic dimeric guanosine monophosphate), to make a vital choice: whether to stay in one place and form a biofilm, or to leave it in search of better conditions. The c-di-GMP network has a bow-tie shaped architecture that integrates many signals from the outside world-the input stimuli-into intracellular c-di-GMP levels that then regulate genes for biofilm formation or for swarming motility-the output phenotypes. How does the 'uninformed' process of evolution produce a network with the right input/output association and enable bacteria to make the right choice? Inspired by new data from 28 clinical isolates of Pseudomonas aeruginosa and strains evolved in laboratory experiments we propose a mathematical model where the c-di-GMP network is analogous to a machine learning classifier. The analogy immediately suggests a mechanism for learning through evolution: adaptation though incremental changes in c-di-GMP network proteins acquires knowledge from past experiences and enables bacteria to use it to direct future behaviors. Our model clarifies the elusive function of the ubiquitous c-di-GMP network, a key regulator of bacterial social traits associated with virulence. More broadly, the link between evolution and machine learning can help explain how natural selection across fluctuating environments produces networks that enable living organisms to make sophisticated decisions.

Pubmed ID: 28767643

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI103369
  • Agency: NIAID NIH HHS, United States
    Id: SC1 AI107955

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Thermo Fisher Scientific (tool)

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An independent federal agency created by Congress to promote the progress of science; to advance the national health, prosperity, and welfare; to secure the national defense They are the funding source for approximately 20 percent of all federally supported basic research conducted by America''s colleges and universities. In many fields such as mathematics, computer science and the social sciences, NSF is the major source of federal backing. NSF leadership has two major components: a director who oversees NSF staff and management responsible for program creation and administration, merit review, planning, budget and day-to-day operations; and a 24-member National Science Board (NSB) of eminent individuals that meets six times a year to establish the overall policies of the foundation.The director and all Board members serve six year terms. Each of them, as well as the NSF deputy director, is appointed by the President of the United States and confirmed by the U.S. Senate. At present, NSF has a total workforce of about 2,100 at its Arlington, Va., headquarters, including approximately 1,400 career employees, 200 scientists from research institutions on temporary duty, 450 contract workers and the staff of the NSB office and the Office of the Inspector General. NSF is the only federal agency whose mission includes support for all fields of fundamental science and engineering, except for medical sciences. They are tasked with keeping the United States at the leading edge of discovery in areas from astronomy to geology to zoology. So, in addition to funding research in the traditional academic areas, the agency also supports high-risk, high pay-off ideas, novel collaborations and numerous projects that may seem like science fiction today, but which the public will take for granted tomorrow. And in every case, they ensure that research is fully integrated with education so that today''s revolutionary work will also be training tomorrow''s top scientists and engineers NSF''s task of identifying and funding work at the frontiers of science and engineering is not a top-down process.

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