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C00002 00002 Data base should contain:
C00005 00003 Tasks:
C00006 00004 Methods:
C00007 00005 Pie in the Sky ideas:
C00009 00006 Further thoughts & Criticisms
C00010 00007 New Ideas - 17-June
C00013 ENDMK
Cā;
Data base should contain:
Known global transformations of DNA over evolution
Details: Which sequences transformed into what
What this meant, phenotypically
Possible path towards this end (ie what local metamorphises)
Time required for each step en route
Possible global (overall environmetal) causes
Known local transformations of DNA
Details: Which sequences transformed into what
If this might imply any phenotypical change
Time required for this
Possible specific causes (ie pH, or some enzyme) - Mechanism
**** Probably more levels than just these two ****
Unexplained transformations - before/after pairs of sequences
Expected transformations - before/after pairs of sequence-categories,
with Mechanism(s)
Examples: These tie into above transformations
Mechanisms: These tie into above transformations
Facilities:
Search for similarities between two before/after pairs
Attempt to explain a before/after pair in terms of a set of mechanisms
Differencing routines -- to describe similarities/differences between a
pair of sequences
It should know which are significant - ie generate a different AA
Perhaps it should use more global information - if "AA-1 AA-2" is
functionally quite analogous to "AA-1 AA-3", the bp change changing
AA-2 to AA-3 may not be considered that relevant, and so on.
Rules which determine [most likely] significant characteristics of a sequence
(see above for defination of significant)
Clustering facility - to note rules of the form change-like-X must be
accompanied with change-like-Y, when the "likes" are similar.
Primitives:
Transformation rules for CS language, capable of full bread-first search
Tasks:
[All use Database and facilities defined above]
1) Given:
DNA sequences A and B
Deduce:
Plausible mechanism(s) for deriving B from A,
[using transformations given in DB, or appropriate analogs]
Answer should include assumptions which had to be fulfilled en route
2) Given:
DNA sequences A and C
Deduce:
A DNA sequences B s.t.
ā plausible mechanism(s) for deriving A from B, and C from B
noting where B-A line split from B-C line
[using procedure defined above]
Answer should include assumptions which had to be fulfilled en route,
and possibly cause for bifircation
Methods:
For Task#1:
Deduce similarities and differences between A and B.
For each difference, determine set of plausible mechanisms
Attempt to find some consistent set from (ā), which mutually require
similar preconditions, and satisfy all global constraints.
Here one may be forced to suggest a transformation which is analogous
to some known change.
For Task#2:
Deduce similarities and differences between A and C
Attempt to explain differences in terms of some sub-part of (proposed) B
which might lead to both A and C.
(Set Task#1 on A - B, and C - B).
Pie in the Sky ideas:
Be able to produce rules for Context Sensitive Language,
derived from examples shown
Design an (General Purpose) Analog Routines: Finds x s.t. A:B :: C:x .
(given A,B,C)
This should be able to apply to, say sequences A,B,C; and to concepts,
and mechanisms, and so on.
Interface with Stefik's system:
When mechanism is acceptable, design an experiment to investigate it.
It could be used to decide which of 2 schemes seem more tractable
[By letting his algorithm decide which to use]
Measure of chance this might happen:
a priori - based on (1) structure of DNA so far
(2) likelihood of this alteration, in general
a posteriori - based on viability of the resultant organism -
[this should consider pathway, and check each intermediate]
Factors should include:
Rate of mutation is feasible, both in DNA sequence & phenotypical changes
Further thoughts & Criticisms
1) DBL: criteria for viability - both overall, & at each stage throughout
2) STT: Method for deciding on strategy - ala Means-Ends Analysis,
to attempt to decide in which manner to attempt to solve this puzzle
3) Some criteria for difficulty - perhaps some meaningful measure
Perhaps tied with a metric between sequences, (or transformation-types)
New Ideas - 17-June
1. Biochemistry related
a) Propose (and "verify") a better mechanism than (Turing-machine-like) Ribosome
-- for going from DNA to protein (or other, better effector?)
[Consider this mechanism to be a local maximum, sufficient for any given
task, but sub-optimal.]
b) Hypothesize a general purpose bacteria, which can "eat" anything [by digesting
whatever is most available... has many local matchers, which trigger things
which might digest it. Store result of this, together with trials, ...
[This essentially experiments, ala MOLGEN - but in real life.]
c) Propose slew of mechanisms which might account for ... and show how easily this
accounts for this effect.
d) For simulating: Modelling vs Reasoning [note RWW SIMULATION structures]
2. Large number of (small caches of) domain facts -- then try to do analogy.
3. Programming - perhaps better formalization -- see MRG
4. Music ? - patterns on patterns. (small deciphering task for RLL, to determine
whether Mozart or Bach wrote X.) Generation? Levels of characteristics...
Talk with Stefik, Brutlag
1) What knowledge is available, and in what form.
Ala Rheumatic DB?; library of genes (including mechanisms?)
2) What are non-trivial tasks, for molecular biology? What are the good
theses?