An Introduction to Systems Biology by Uri Alon in 2020
systems biology, network inference, dynamical systems
Part 1. Network motifs
1. Transcription networks: basic concepts
- 1.1 Introduction
- 1.2 The cognitive problem of the cell
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1.3 Elements of transcription networks
- 1.3.1 Separation of timescales
- 1.3.2 The signs on the arrows: activators and repressors
- 1.3.3 The numbers on the arrows: input functions
- 1.3.4 Logic input functions: a simple framework for understanding network dynamics
- 1.3.5 Multi-dimensional input functions govern genes with several inputs
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1.4 Dynamics and response time of simple regulation
- 1.4.1 The response time of stable proteins is one cell generation
2. Autoregulation: a network motif
- 2.1 Introduction
- 2.2 Patterns, randomized networks, and network motifs
- 2.3 Autoregulation is a network motif
- 2.4 Negative autoregulation speeds the response time of gene circuits
- 2.5 Negative autoregulation promotes robustness to fluctuations in production rate
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2.6 Summary: evolution as an engineer
- Negative autoregulation is a network motif, a pattern that recurs throughout the network at numbers much higher than expected in random networks. To understand why negative autoregulation is a network motif, we asked what functions it can perform.
- The second (NAR) design has the advantage that the goal, \[X_{st}\], is reached faster. Furthermore, the fluctuations around \[X_{st}\] due to variations in production and removal rate are reduced in the second, autoregulated design.
- In an imaginary competition between two species are identical except that one uses circuit A, and the second uses circuit B, the latter would have a selective advantage. Over evolutionary times, structures that have engineering advantages would tend to be selected and appear as network motifs.
3. The feedforward loop network motif
- 3.1 Introduction
- 3.2 The feedforward loop is a network motif
- 3.3 The structure of the feedforward loop gene circuit
- 3.4 Dynamics of the coherent Type-1 FFL with AND logic
- 3.5 The C1-FFL is a sign-sensitive delay element
- 3.6 OR-gate C1-FFL is a sign-sensitive delay for off steps
- 3.7 The incoherent Type-1 FFL generates pulses of output
- 3.8 The other six FFL types can also act as filters and pulse generators
- 3.9 Convergent evolution of FFLs
- 3.10 Summary
4. Temporal programs and the global structure of transcription networks
- 4.1 Introduction
- 4.2 The single-input module (SIM) network motif
- 4.3 The SIM can generate temporal gene expression programs
- 4.4 The multi-output feedforward loop
- 4.5 The multi-output FFL can generate FIFO temporal programs
- 4.6 Signal integration by BI-FANS and dense-overlapping regulons
- 4.7 Network motifs and the global structure of sensory transcription networks
- 4.8 Interlocked feedforward loops in the B. subtilis sporulation network
5. Positive feedback, bistability, and memory
- 5.1 Network motifs in developmental transcription networks
- 5.2 Network motifs in protein-protein interaction networks