chemart / typogenetics

hub:
  repo_type: generator
  builtin: typogenetics
  tags:
  - banzhaf-yamamoto
chemistries:
- id: typogenetics
  name: Typogenetics
  intuition: 'Strands that code the enzymes which act on strands. A strand over A, C, G, T is read two
    letters at a time into a sequence of operations - cut, copy, move, insert - and the resulting enzyme''s
    shape determines which base it binds to, so the strand determines what happens to strands. Self-replicators
    exist and are built as inverted repeats. Variable molecule length, a variable number of products and
    non-deterministic binding make it a genuine stress test for anything that computes closures.

    '
  aliases:
  - typographical genetics
  origin: Hofstadter, 1979; Morris, 1989; Varetto, 1993
  book: 10.5.2; lock-and-key 11.2
  refs:
  - '[391]'
  - '[482]'
  - '[597]'
  - '[598]'
  - '[882]'
  - '[883]'
  - '[785]'
  family: automata
  kind: generator
  constructive: true
  S:
    repr: single strands over {A, C, G, T}; species id is the strand itself, structure the enzymes it
      codes with their binding base ('cop-swi-rpu-ina-swi-cop:G'). Double strands exist only while enzymes
      work and fall apart into single strands at the end
    definition: implicit
  R:
    definition: implicit
    arity: 1 (reaction self, the book's self-reactions) or 2 (reaction pair)
    scheme: 'self: s -> daughters(s); pair: g + s -> g + daughters of s under the enzymes of g. The strand
      is translated duplet by duplet into typoenzymes (AA separates enzymes); each enzyme binds a unit
      holding its preferred base (fixed by the kinks s/l/r of its amino acids) and runs cut, del, swi,
      mvr, mvl, cop, off, ina, inc, ing, int, rpy, rpu, lpy, lpu on a two-row complex; the rows then separate
      into daughters.

      '
    notes: 'Enzymes of one strand run in translation order, each binding in the stretch where the previous
      one stopped (Snare 1999, 2.6). Hofstadter lets an enzyme bind any matching unit, so one strand can
      have several outcomes; binding_tiebreak all makes each outcome a separate reaction. A reaction that
      leaves the reactants unchanged (no binding site, or a trivial enzyme) is elastic and not listed.

      '
  A:
    reactor:
    - sequential-vm
    - well-stirred-multiset
    dilution: 'closure: none; soup: a random molecule is removed after each productive event, keeping
      the population size constant (Chemart addition)'
    notes: The book's system interprets strands one at a time (10.5.2). Varetto's simulations with limited
      resources and a lethal factor are not reproduced
  params:
  - name: method
    type: enum
    default: closure
    choices:
    - closure
    - soup
    role: structural
    meaning: 'closure: every reaction reachable from the seed strands (status complete or truncated);
      soup: random draws from a population with chemart.soup, returning the reactions that fired with
      counts (status observed)'
  - name: reaction
    type: enum
    default: self
    choices:
    - self
    - pair
    role: structural
    meaning: 'self: a strand''s enzymes act on the strand itself (book 10.5.2, Hofstadter''s puzzle);
      pair: the enzymes of the first strand act on the second, which is consumed, while the gene strand
      is a catalyst (Chemart addition)'
  - name: code_table
    type: enum
    default: hofstadter
    choices:
    - hofstadter
    - varetto
    role: structural
    meaning: 'duplet -> amino acid table: hofstadter (GEB p. 510, book table 10.1 left) or varetto (Varetto
      1993 p. 187 as given by Snare table 2.1b: GA inc, GC ing, GG int, GT ina, kinks s, r, r, l stay
      with the columns)'
  - name: fold
    type: enum
    default: hofstadter
    choices:
    - hofstadter
    - morris
    role: structural
    meaning: 'binding preference from the kinks: hofstadter counts the kinks of all amino acids but the
      first and last (GEB p. 511); morris counts every kink (Morris 1989, Varetto 1993, book fig. 10.6).
      Last segment relative to the first: straight A, up (left turn) C, down (right turn) G, back T'
  - name: binding_tiebreak
    type: enum
    default: all
    choices:
    - all
    - random
    - leftmost
    - rightmost
    range: 'Hofstadter and Morris: any matching unit (all or random); Varetto: rightmost'
    role: stochastic
    meaning: 'which unit an enzyme binds when several hold its base: all lists every outcome as its own
      reaction (closure only), random draws one with the generator, leftmost/rightmost take the first/last
      in the bound strand''s reading direction'
  - name: strands
    type: list
    default:
    - CGATTCGAATCG
    range: Snare's self-replicators CGATTCGAATCG and CGATTAATTAATCG; GEB's TAGATCCAGTCCATCGA
    role: structural
    meaning: seed strands (closure) or the strand types of the initial population (soup); an empty list
      draws n_random random strands of strand_length bases
  - name: n_random
    type: int
    default: 4
    min: 1
    max: 1000
    role: population
    meaning: number of random seed strands when strands is empty
  - name: strand_length
    type: int
    default: 12
    min: 1
    max: 200
    role: structural
    meaning: length of the random seed strands when strands is empty
  - name: max_length
    type: int
    default: 24
    min: 1
    max: 1000
    role: structural
    meaning: longest daughter strand kept; an outcome with a longer daughter is dropped (closure status
      truncated, elastic in the soup)
  - name: max_species
    type: int
    default: 200
    min: 1
    max: 100000
    role: structural
    meaning: 'closure only: species budget; the status becomes truncated when it cuts the closure off'
  - name: max_branches
    type: int
    default: 1000
    min: 1
    max: 1000000
    role: structural
    meaning: 'binding_tiebreak all: most distinct intermediate complexes followed while enumerating binding
      choices for one reactant; beyond it that reactant''s reactions are dropped and the status becomes
      truncated'
  - name: copies
    type: int
    default: 50
    min: 1
    max: 100000
    role: population
    meaning: 'soup only: copies of each seed strand in the initial population, whose size the soup keeps
      constant'
  - name: steps
    type: int
    default: 2000
    min: 0
    max: 10000000
    role: stochastic
    meaning: 'soup only: number of draws (one strand for self, an ordered gene/target pair for pair)'
  provides:
  - topology
  - stoichiometry
  - catalysts
  - flow
  - initial-state
  - sequence-structure-function
  fidelity: reconstructed
  sources:
  - 'Banzhaf & Yamamoto (2015), 10.5.2: table 10.1 (code and kinks) and fig. 10.6 (the two-enzyme reaction
    of CGACCCAACGATTTTTCAT with products CGACCCAACG, ATTTTTCAT, CGTTGGGT, from Morris [597]).'
  - 'Snare, A. (1999). Typogenetics. BSc (Hons) thesis, School of Computer Science and Software Engineering,
    Monash University (book ref [785]): chapter 2 (a specification reconciling Hofstadter, Morris and
    Varetto: tables 2.1-2.2, the amino-acid semantics, self-application rules), 3.2-3.3 (dud and self-replicating
    strands) and appendix A.1 Typogenetics.py. http://web.archive.org/web/2005id_/http://www.csse.monash.edu.au/hons/projects/1999/Andrew.Snare/thesis.pdf'
  - 'Hofstadter''s GEB (1979) chapter examples (pp. 508-511) as reproduced by independent implementations,
    used to cross-check the table, kinks and the worked example: kortschak/typo (Go; https://github.com/kortschak/typo,
    Example_book and TestOperateOn), mkpankov/typogenetics (Python; https://github.com/mkpankov/typogenetics,
    testACopyingTranslationByStage), palm86/typogenetics (Elixir; https://github.com/palm86/typogenetics,
    preference test), lechimp-p/Typogenetics (Haskell; https://github.com/lechimp-p/Typogenetics).'
  decisions:
  - GEB itself, Morris [597, 598] (the UBC thesis page blocked downloads), Varetto [882, 883] and Kvasnicka
    et al. [482] (author links dead, not in the Wayback Machine) were not accessible. The machine follows
    Snare's specification, checked against the book's fig. 10.6 and against GEB's worked example as reproduced
    by three independent implementations.
  - 'Code table: Hofstadter''s table agrees in book table 10.1, Snare table 2.1a and all four implementations
    (kinks included). Book table 10.1 prints the same table twice although the caption says the right
    one is Varetto''s (erratum); the varetto choice uses Snare table 2.1b, which only permutes the insert
    amino acids of row G and keeps the kinks with the columns. Its only source here is Snare.'
  - 'Binding preference: fold hofstadter counts the kinks of amino acids 2..n-1 (Snare 2.4 and Typogenetics.py;
    GEB p. 511 gives rpy-ina-rpu-mvr-int-mvl-cut-swi-cop preference C). fold morris counts all kinks,
    which is what book fig. 10.6 needs (cop-cut-mvl binds G, cop-swi-lpu-lpu-mvr binds A). A single-amino-acid
    enzyme binds A under fold hofstadter (Snare''s choice; GEB is silent).'
  - GEB's worked example (p. 508) binds rpu-inc-cop-mvr-mvl-swi-lpu-int at the middle G of TAGATCCAGTCCATCGA.
    Under fold hofstadter that enzyme prefers T and under fold morris A, so the example's binding site
    is taken as given, not derived (kortschak's implementation derives G from a third kink-counting rule
    that contradicts p. 511).
  - An inserting amino acid (ina/inc/ing/int) puts the base to the right of the bound unit and moves the
    enzyme onto it, with the complementary base opposite in copy mode and a gap otherwise; this reproduces
    GEB's worked example (products ATG and TAGATCCAGTCCACATCGA). Snare's code keeps the enzyme on the
    old unit, which gives GTT and TAGATCCAGTCCAACTCGA instead.
  - 'Other semantics as in Snare: cut severs both rows right of the bound unit and the enzyme continues
    on the left part (fig. 10.6); del leaves a gap (keeping the rows aligned, unlike Morris'' shifting
    del) and moves right; mvr/mvl/swi into a gap or off the end stop the enzyme; rpy/rpu/lpy/lpu cross
    a gap in one row but not in both, and bases filled in by copy mode on the way do not end the search
    (fig. 10.6 needs this); on the upper strand left and right are reversed.'
  - 'Self-application (Snare 2.6): enzymes run in translation order; each binds in the gap-free stretch
    of the row where the previous enzyme stopped, and copy mode is reset between enzymes. An enzyme with
    no site is skipped and the next one starts from the same position (Snare''s code resets the position
    to 0 there).'
  - binding_tiebreak all enumerates every binding choice of every enzyme and gives one reaction per distinct
    multiset of daughters; with random the closure samples one outcome per reactant (fixed by the seed),
    the soup a fresh one per draw. leftmost/rightmost are in the bound strand's reading direction; rightmost
    is Varetto's rule (Snare 2.4).
  - 'Stoichiometry: in self the strand is consumed and its daughters are produced (a self-replicator is
    s -> 2 s, so s shows as a catalyst); in pair the gene strand is translated without being consumed
    and appears on both sides. The book''s fig. 10.6 caption (''enzymes coded by the strand operate on
    a copy of the same strand'') fits pair with g = s, whose reaction is 2 s -> s + daughters. No rates
    are published, so rates are None.'
  - Species are single strands; double-stranded complexes are intermediate states inside a reaction and
    always separate at the end, as in GEB's puzzle and Snare's extractstrands. The v1 strand_length is
    kept only for random seeds; lethal_factor is dropped because Varetto's definition was not accessible.
  - 'Truncation: strands can grow by insertion, so max_length drops outcomes with longer daughters and
    max_branches bounds the enumeration of binding choices; either makes the closure status truncated.'
  - 'Soup (Chemart addition): chemart.soup with constant dilution; a random molecule is removed after
    each productive event, so outflow is constant-total. Hofstadter''s generational puzzle (every strand
    replaced by its daughters each generation) is not a separate method.'
  reference_impl: Snare (1999) Typogenetics.py (appendix A.1 of the thesis); kortschak/typo (Go)
  phenomena:
  - 'self-replicating strands built as inverted repeats: CGATTCGAATCG and CGATTAATTAATCG -> 2 copies when
    their enzyme binds the rightmost G (Snare 3.3, fig. 3.2)'
  - dud strands whose enzymes find no binding site (CGGC codes cop-inc, which binds A; Snare 3.1.1)
  - a single reaction yields a variable number of products and, with free binding choice, several alternative
    outcomes (book 10.5.2, fig. 10.6)
  - short self-replicators growing exponentially and autocatalytic 'tanglecycles' in Varetto's modified
    system (book 10.5.2; not reproduced here)
  notes: 'Variable molecule size, variable product count and non-deterministic binding make this a stress
    test for constructive closures. The book''s statement that Varetto''s code table differs is right,
    but its table 10.1 prints Hofstadter''s table on both sides.

    '