1 Connectron Dynamics Richard J. Feldmann Global Determinants, Inc. Derwood, Maryland 20855, USA...
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Transcript of 1 Connectron Dynamics Richard J. Feldmann Global Determinants, Inc. Derwood, Maryland 20855, USA...
1
Connectron Dynamics
Richard J. Feldmann
Global Determinants, Inc.
Derwood, Maryland 20855, USA
2
The goals of the Connectron Dynamics Examples
To show how simple Connectron patterns can build up complex gene and non-coding RNA transcription behaviors
To develop a conceptual framework for analyzing the behavior of large eukaryotic transcriptomes.
3
How the Connectron Dynamics Examples work
Rules determine which gene or non-coding RNA causes the repression of transcription of which other genes or non-coding RNAs.
The graphic present the rules in a visual form. The “music score” is the result of the simulation
of the behavior of the rules. The sound is the “music” of the simulation.
4
g/nc 1Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 0 -
State = 100####################################################################################################
The transcription of a single gene or non-coding RNAis controlled only the transcription factors
5
g/nc 1 g/nc 2Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 0 - 2 10 3 0 -
State = 100########################################################################################################################################################################################################
The transcription of two genes or non-coding RNAsis controlled independently by their transcription factors
6
g/nc 1
5
g/nc 2Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 1 - 2 2 10 3 0 -
State = 100#####################################################################################################...................................................................................................
A genes or non-coding RNA that generates a Connectron turns off the transcription of another gene or non-coding RNA
7
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 1 - 1
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...
g/nc 1
5
A gene or non-coding RNA can use a Connectronto turn off its own transcription.
8
Connectron Dynamics
Input Structure
i | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 10 3 0 -
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...
g/nc 1
5
g/nc 2
5
A “one-shot” connectron can turn off the transcriptionof another gene or non-coding RNA.
9
1
5
2
10
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 1 - 1 2 10 3 1 - 2
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...###..........#..........#..........#..........#..........#..........#..........#..........#.........
Two one-shot Connectrons transcribe independently.
10
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 10 3 1 - 2
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...#.....#...........#...........#...........#...........#...........#...........#...........#.........
g/nc 1
5
g/nc 2
10
5
One one-shot Connectron can drive another one-shot Connectron
11
Connectron Dynamics
Input Structure
i | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 1 - 2
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...#.....#.................#.................#.................#.................#.................#...
g/nc 1
5
g/nc 2
12
5
Changing the lifetime of the second one-shot Connectronchanges the “music” of the behavior
12
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 3 3 1 - 2
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...
g/nc 1
5
g/nc 2
3
5
A short lifetime of the second one-shot locks its behaviorto the driving one-shot.
13
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 7 3 1 - 2
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...#.....#...........#...........#...........#...........#...........#...........#...........#.........
g/nc 1
5
g/nc 2
7
5
Playing with the lifetimes produces different behaviors.
14
g/nc 1
5
g/nc 2
12
5
g/nc 3
20
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 1 - 2 3 20 3 1 - 3
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...#.....#.................#.................#.................#.................#.................#...###....................#....................#....................#....................#.............
A third one-shot runs independently
15
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 1 - 2 3 20 3 2 - 3 2
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...#...................................................................................................###....................#....................#....................#....................#.............
g/nc 1
5
g/nc 2
12
5
g/nc 3
20
20
Coupling the one-shots produces a particular behavior.
16
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 1 - 1 2 12 3 1 - 2 3 20 3 2 - 3 2
State = 100#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#.....#...###....................#....................#....................#....................#.............###....................#....................#....................#....................#.............
g/nc 1
5
g/nc 2
12
g/nc 3
20
20
Playing with the connectivity produces different behaviors.
17
g/nc 1
5
g/nc 2
12
5
g/nc 3
20
20
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 1 - 2 3 20 3 2 - 3 1
State = 100#......................#....................#....................#....................#.............#.....#............#............#.................#............#............#...............#.......###....................#....................#....................#....................#.............
This coupling produces an interesting behavior.
18
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 1 - 2 3 7 3 2 - 3 1
State = 100#.........#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.#.....#.................#...............#...............#...............#...............#...........###.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.
g/nc 1
5
g/nc 2
12
5
g/nc 3
7
7
Playing with the lifetimes produces another behavior.
19
g/nc 1
5
g/nc 2
12
5
g/nc 3
20
20
g/nc 4
5
g/nc 5
12
5
g/nc 6
7
7
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 1 - 2 3 20 3 2 - 3 1 4 5 0 2 - 4 5 5 12 3 1 - 5 6 7 3 2 - 6 4
State = 100#......................#....................#....................#....................#.............#.....#............#............#.................#............#............#...............#.......###....................#....................#....................#....................#.............#.........#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.#.....#.................#...............#...............#...............#...............#...........###.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.
The two sets of one-shotConnectrons are runningindependently.
20
g/nc 1
5
g/nc 2
12
5
g/nc 3
20
20
g/nc 4
5
g/nc 5
12
5
g/nc 6
7
7
12
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 2 - 2 4 3 20 3 2 - 3 1 4 5 0 2 - 4 5 5 12 3 1 - 5 6 7 3 2 - 6 4
State = 100#......................#....................#....................#....................#.............#.....#............#............#.................#............#............#...............#.......###....................#....................#....................#....................#.............#.................................................#.......................................#.........#.....#............#............#............#............#............#............#............#..###.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.
Two sets of three one-shotscoupled together producesan interesting behavior.
21
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 2 - 2 6 3 20 3 2 - 3 1 4 5 0 2 - 4 5 5 12 3 1 - 5 6 7 3 2 - 6 4
State = 100#......................#....................#....................#....................#.............#.....#............#............#.................#............#............#...............#.......###....................#....................#....................#....................#.............#.........#.....#..........#............#............#.....#...........#............#............#..#.....#...............#............#............#................#............#............#........###................#............#............#.................#............#............#..........
g/nc 1
5
g/nc 2
12
5
g/nc 3
20
20
g/nc 4
5
g/nc 5
12
5
g/nc 6
7
7
12
This coupled behavioris quite different.
22
Connectron Dynamics
Input Structure
i | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 2 - 2 4 3 20 3 2 - 3 1 4 5 0 2 - 4 5 5 12 3 1 - 5 6 7 3 2 - 6 4 7 5 0 2 - 7 8 8 12 3 2 - 8 12 9 20 3 2 - 9 7 10 5 0 2 - 10 11 11 12 3 1 - 11 12 7 3 2 - 12 10
State = 100#......................#....................#....................#....................#.............#.....#............#............#.................#............#............#...............#.......###....................#....................#....................#....................#.............#.................................................#.......................................#.........#.....#............#............#............#............#............#............#............#..###.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.#......................#....................#....................#....................#.............#.....#............#............#.................#............#............#...............#.......###....................#....................#....................#....................#.............#.........#.....#..........#............#............#.....#...........#............#............#..#.....#...............#............#............#................#............#............#........###................#............#............#.................#............#............#..........
g/nc 1
5
g/nc 2
12
5
g/nc 3
20
20
g/nc 4
5
g/nc 5
12
5
g/nc 6
7
7
12
g/nc 7
5
g/nc 8
12
5
g/nc 9
20
20
g/nc 10
5
g/nc 11
12
5
g/nc 12
7
7
12
Two sets of six one-shots running independently.
23
g/nc 1
5
g/nc 2
12
5
g/nc 3
20
20
g/nc 4
5
g/nc 5
12
5
g/nc 6
7
7
12
g/nc 7
5
g/nc 8
12
5
g/nc 9
20
20
g/nc 10
5
g/nc 11
12
5
g/nc 12
7
7
12
20
Connectron Dynamics
Input Structure
gene/non-coding RNA | duration | | offset | | | num of connections | | | | first connection | | | | | second connection | | | | | | 1 5 0 2 - 1 2 2 12 3 2 - 2 4 3 20 3 2 - 3 1 4 5 0 2 - 4 5 5 12 3 1 - 5 6 7 3 2 - 6 4 7 5 0 2 - 7 8 8 12 3 2 - 8 12 9 20 3 2 - 9 7 10 5 0 2 - 10 11 11 12 3 1 - 11 12 7 3 2 - 12 10
State = 100#......................#....................#....................#....................#.............#.....#............#............#.................#............#............#...............#.......###....................#....................#....................#....................#.............#.................................................#.......................................#.........#.....#............#............#............#............#............#............#............#..###.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.......#.#......................#....................#....................#....................#.............#.....#............#............#.................#............#............#...............#.......###....................#....................#....................#....................#.............#.........#.....#..........#............#............#.....#...........#............#............#..#.....#...............#............#............#................#............#............#........###................#............#............#.................#............#............#..........
The four sets of Connectrons are coupledthus producing a very interesting behavior.
24
The Connectrome of a “Toy” Genome
Chromosome 1
Chromosome 2 Chromosome 4
1
5
2
12
5
3
20
20
4
5
5
12
5
6
7
7
12
7
5
8
12
5
9
20
20
10
5
11
12
5
12
7
7
1220
Chromosome 3
25
The Connectrome of the Transcriptome of the Mouse Genome
Cross Chromosome Table = 1Both Gene and Non-Coding Gene Driven ConnectronsBoth U/D and L/R ConnectronsValues divided by 1000
Receiving Chromosome - T1-T2 X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 | | | | | | | | | | | | | | | | | | | | | | 1 - 9 .533 .577 1 .577 .625 .737 .504 .447 .778 .252 .387 .578 .549 .249 .318 .550 .625 .118 1 1 2 - .410 33 .538 .372 .351 .436 .415 .255 .210 .407 .142 .234 .319 .184 .199 .205 .340 .375 .103 .996 .491 3 - .321 .189 9 .625 .345 .367 .534 .345 .423 .535 .177 .278 1 .299 .186 .197 .365 .486 .063 1 1 4 - .300 .169 .211 490 .417 1 .402 .253 .369 .555 .387 .278 .339 .339 .116 .242 .644 .465 .082 1 .519 5 - .351 .359 .214 .186 53 .359 .367 .298 .307 .564 .246 .399 .441 .355 .213 .813 .392 .458 .078 2 .778 6 - .267 .182 .259 .664 .197 14 .507 .236 .344 .448 .133 .238 2 .233 .170 .201 .245 .352 .092 1 1 7 - .359 .114 .249 .103 .397 .211 259 .210 .263 .313 .155 .333 .397 .246 .079 .170 .360 .295 .037 1 .347 8 - .274 .110 .238 .337 .097 .182 .228 10 .311 .209 .123 .200 .296 .119 .129 .131 .426 .229 .056 .857 .034 9 - .431 .275 .311 .795 .140 .307 .440 .232 10 .354 .178 .363 .884 .201 .188 .228 .576 .359 .076 1 .649 10 - .345 .161 .175 .234 .368 .220 .286 .184 .261 5 .244 .573 .446 .255 .160 .196 .446 .435 .116 23 .170 11 - .347 .157 .210 .140 .154 .233 .399 .233 .227 .200 12 .270 .930 .214 .151 .190 .747 .307 .074 .898 .138 12 - .369 .181 .291 .196 .144 .306 .324 .147 .177 .229 .126 283 .432 .239 .094 .181 .327 .278 .026 1 .266 13 - .182 .124 .156 .117 .109 .186 .154 .238 .139 .238 .073 .114 19 .172 .113 .137 .228 .306 .066 .941 .163 14 - .067 .087 .131 .123 .085 .107 .104 .095 .153 .126 .250 .116 .075 15 .072 .064 .275 .242 .052 .897 .442 15 - .160 .131 .135 .472 .111 .136 .219 .149 .130 .115 .090 .092 .086 .040 10 .114 .085 .167 .058 1 .532 16 - .219 .033 .161 .102 .068 .149 .144 .115 .235 .177 .079 .092 .242 .075 .041 2 .481 .278 .060 3 1 17 - .191 .049 .115 .040 .087 .093 .094 .146 .115 .195 .140 .077 .102 .621 .035 .099 34 .222 .065 1 1 18 - .163 .060 .239 .226 .092 .129 .127 .115 .101 .196 .088 .089 .170 .078 .144 .069 .092 13 .059 .543 .411 19 - .149 .069 .117 .037 .090 .117 .064 .105 .107 .178 .087 .101 .142 .063 .035 .091 .100 .180 6 .786 .243 20 -X 21 - .169 .131 .158 .074 .119 .173 .202 .103 .157 .193 .101 .115 .174 .074 .080 .176 .082 .195 .044 472 51Y 22 - .001 .010 2 554 | | | | | | | | | | | | | | | | | | | | | | 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 | Emitting Chromosome - C1-C2
C1-C2 sum = 2665 T1-T2 sum = 2665