[FOM] "Proofs of life"
Rene Vestergaard
renevestergaard at acm.org
Tue Nov 6 20:37:50 EST 2018
"Proofs of life: molecular-biology reasoning simulates cell behaviors
from first principles" is now available at http://arxiv.org/abs/1811.02478
The work springs from computer-verified reasoning and establishes wider
utility by means of a reasoning-computation correspondence, including
for long-standing critical problems in biology that have defied standard
approaches.
Sincerely,
Rene
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ESSENCE
Mathematics-style correctness works for molecular biology and enables
phenotype and life-cycle prediction from genotypes. Formally,
reductionist science involves constructive reasoning, i.e., executable
simulation.
SIGNIFICANCE
Axiomatic reasoning provides an alternative perspective that allows us
to address long-standing open problems in biology. Our approach is
supported by meta-theory and likely applies to any reductionist discipline.
ABSTRACT
Science relies on external correctness: statistical analysis and
reproducibility, with ready applicability but inherent false
positives/negatives. Mathematics uses internal correctness: conclusions
must be established by detailed reasoning, with high confidence and deep
insights but not necessarily real-world significance. Here, we formalize
the molecular-biology reasoning style; establish that it constitutes an
executable first-principle theory of cell behaviors that admits
predictive technologies, with a range of correctness guarantees; and
show that we can fully account for the standard reference: Ptashne, A
Genetic Switch. Everything works for principled reasons and is presented
within an open-ended meta-theoretic framework that seemingly applies to
any reductionist discipline. The framework is adapted from a
century-long line of work on mathematical reasoning. The key step is to
not admit reasoning based on an external notion of truth but work only
with what can be justified from considered assumptions. For molecular
biology, the induced theory involves the concurrent running/interference
of molecule-coded elementary processes of physiology change over the
genome. The life cycle of the single-celled monograph organism is
predicted in molecular detail as the aggregate of the possible
sequentializations of the coded-for processes. The difficult question of
molecular coding, i.e., the specific means of gene regulation, is
addressed via a detailed modeling methodology. We establish a
complementary perspective on science, complete with a proven correctness
notion, and use it to make progress on long-standing and critical open
problems in biology.
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