molecular simulations of dna loop extrusion explain and
play

Molecular simulations of DNA loop extrusion explain and predict - PowerPoint PPT Presentation

Aug 25, 2023 •116 likes •1.48k views

Molecular simulations of DNA loop extrusion explain and predict human genome architecture Adrian Sanborn Stanford University; The Center for Genome Architecture at Baylor College of Medicine, Rice University FUNDAMENTAL PUZZLE: SAME GENOME

  1. Molecular simulations of DNA loop extrusion explain and predict human genome architecture Adrian Sanborn Stanford University; The Center for Genome Architecture at Baylor College of Medicine, Rice University

  2. FUNDAMENTAL PUZZLE: SAME GENOME à DIFFERENT FUNCTIONS

  3. THE GENOME IS FULL OF “SPOOKY ACTION AT A DISTANCE”

  4. THE GENOME IS FULL OF “SPOOKY ACTION AT A DISTANCE”

  5. THE HUMAN GENOME IS LONG 3 BILLION LETTERS 2 METERS …CGTTTACGAAAATCGCAAAACTTTCGATACCCATAGGCTACTGATCATACGACCGTTTACGAAAATCGAAACCTTTCCGATCTAGGCTAC… Nucleus Cell 6 μm

  6. 100 Mb 10 Mb 1 Mb 100 Kb 10 Kb 1 Kb 100 bp 10 bp

  7. 100 Mb 10 Mb 1 Mb 100 Kb 10 Kb 1 Kb 100 bp 10 bp

  8. HOW DOES THE GENOME FOLD? 1. Experimental Technology 2. Biology 3. Physics

  9. PART I: 
 EXPERIMENTAL TECHNOLOGY

  10. MICROSCOPY & FLUORESCENT IN SITU HYBRIDIZATION 
 FISH

  11. MICROSCOPY & FLUORESCENT IN SITU HYBRIDIZATION 
 FISH

  12. HI-C MEASURES SPATIAL PROXIMITY OF THE FOLDED GENOME Lieberman-Aiden, van Berkum et al. Science 2009

  13. CONTACT MAPPING Exploring structure via proximity

  20. SIMPSONS 
 CONTACT MAP # of Pictures Together

  21. HI-C MEASURES SPATIAL PROXIMITY OF THE FOLDED GENOME Lieberman-Aiden, van Berkum et al. Science 2009

  22. HI-C MEASURES SPATIAL PROXIMITY OF THE FOLDED GENOME Lieberman-Aiden, van Berkum et al. Science 2009

  23. Hi-C 
 GENERATES GENOME- WIDE CONTACT MAPS

  24. Hi-C 
 GENERATES GENOME- Chromosome WIDE CONTACT MAPS

  25. Genome Hi-C 
 GENERATES GENOME- WIDE CONTACT MAPS

  26. Genome Hi-C 
 GENERATES GENOME- WIDE CONTACT MAPS

  27. Genome Hi-C 
 GENERATES GENOME- WIDE CONTACT MAPS

  28. Genome Hi-C 
 GENERATES GENOME- WIDE CONTACT MAPS

  29. Hi-C 
 GENERATES GENOME- WIDE CONTACT MAPS

  30. Chromosome 8 Hi-C 
 GENERATES GENOME- WIDE CONTACT MAPS 0 700 Reads/250 kb 2

  31. Hi-C 
 GENERATES GENOME- WIDE CONTACT MAPS 0 700 Reads/250 kb 2

  32. A Hi-C 
 GENERATES GENOME- A WIDE CONTACT MAPS 0 700 Reads/250 kb 2

  33. A Hi-C 
 GENERATES GENOME- A WIDE CONTACT MAPS 0 700 Reads/250 kb 2

  34. A B Hi-C 
 GENERATES GENOME- A WIDE CONTACT MAPS B 0 700 Reads/250 kb 2

  35. NEW CONTACT MAPS ARE AT KILOBASE RESOLUTION 30 million contacts

  36. NEW CONTACT MAPS ARE AT KILOBASE RESOLUTION 30 million contacts 5 billion contacts Rao & Huntley, et al., Cell 2014

  37. PART II: 
 BIOLOGY Mary Ellen Scherl

  38. LOOPS IN CHROMATIN = PEAKS IN A CONTACT MAP A+2 ε B-2 ε A+ ε B- ε A B B+2 ε A-2 ε A- ε B+ ε

  39. LOOPS IN CHROMATIN = PEAKS IN A CONTACT MAP A+2 ε B-2 ε A+ ε B- ε A B B+2 ε A-2 ε A- ε B+ ε

  40. LOOPS IN CHROMATIN = PEAKS IN A CONTACT MAP A+2 ε B-2 ε A+ ε B- ε A B B+2 ε A-2 ε A- ε B+ ε

  41. THE GENOME HAS ~10,000 LOOPS. Rao & Huntley, et al., Cell 2014

  42. THE GENOME HAS ~10,000 LOOPS. Rao & Huntley, et al., Cell 2014

  43. THE GENOME HAS ~10,000 LOOPS. Rao & Huntley, et al., Cell 2014

  44. LOOPS ARE OFTEN CONSERVED ACROSS CELL TYPE…

  45. LOOPS ARE OFTEN CONSERVED ACROSS CELL TYPE…

  46. LOOPS ARE OFTEN CONSERVED ACROSS CELL TYPE… Rao & Huntley, et al., Cell 2014

  47. …AND SPECIES.

  48. …AND SPECIES. Rao & Huntley, et al., Cell 2014

  49. LOOPS TURN GENES ON AND OFF .

  50. LOOPS TURN GENES ON AND OFF . Rao & Huntley, et al., Cell 2014

  51. LOOPS TURN GENES ON AND OFF .

  52. LOOPS TURN GENES ON AND OFF . Rao & Huntley, et al., Cell 2014

  53. LOOPS DEMARCATE CONTACT DOMAINS… Rao & Huntley, et al., Cell 2014

  54. LOOPS DEMARCATE CONTACT DOMAINS… Rao & Huntley, et al., Cell 2014

  55. …WHICH PARTITION THE GENOME

  56. …WHICH PARTITION THE GENOME Rao & Huntley, et al., Cell 2014

  57. HOW DO LOOPS AND DOMAINS FORM?

  58. PART III: 
 PHYSICS

  59. CONTACT PROBABILITY AS A FUNCTION OF GENOMIC DISTANCE

  60. CONTACT PROBABILITY AS A FUNCTION OF GENOMIC DISTANCE

  61. FOLDED DNA IS NOT AT EQUILIBRIUM Erez Lieberman-Aiden, Nynke van Berkum et al. Science 2009

  62. FOLDED DNA IS NOT AT EQUILIBRIUM Erez Lieberman-Aiden, Nynke van Berkum et al. Science 2009

  63. Sanborn & Rao, et al., PNAS, 2015

  64. CONTACT PROBABILITY EXPONENT WITHIN DOMAINS IS -0.75 Sanborn & Rao, et al., PNAS, 2015

  65. CONTACT PROBABILITY EXPONENT WITHIN DOMAINS IS -0.75 Sanborn & Rao, et al., PNAS, 2015

  66. CONTACT PROBABILITY EXPONENT WITHIN DOMAINS IS -0.75 Sanborn & Rao, et al., PNAS, 2015

  67. INTERNAL VERSUS EXTERNAL FORCES Sanborn & Rao, et al., PNAS, 2015

  68. INTERNAL FORCES à LINEAR COLLAPSE Sanborn & Rao, et al., PNAS, 2015

  69. TENSION GLOBULE RECAPITULATES OBSERVED CONTACT PROBABILITY Hi-C Tension globule Sanborn & Rao, et al., PNAS, 2015

  70. INTERNAL FORCES ARE COMPUTATIONALLY INTENSIVE

  71. INTERNAL FORCES ARE COMPUTATIONALLY INTENSIVE Polymer backbone Lennard-Jones forces Simulate Langevin dynamics using LAMMPS package

  72. INTERNAL FORCES ARE COMPUTATIONALLY INTENSIVE • Simulations up to 50,000 beads (50 megabases) • Forces must be calculated between all pairs of beads • Hundreds of replicate structures must be simulated • GPU parallelization à ~10x speed-up

  73. LOOPS AND DOMAINS FORM WITHIN TENSION GLOBULES

  74. LOOPS ARE ANCHORED AT CONVERGENT CTCF SITES

  75. LOOPS ARE ANCHORED AT CONVERGENT CTCF SITES Rao & Huntley, et al., Cell 2014

  76. LOOP FORMATION BY DIFFUSION Sanborn & Rao, et al., PNAS, 2015

  77. LOOP FORMATION BY DIFFUSION Sanborn & Rao, et al., PNAS, 2015

  78. LOOP FORMATION BY DIFFUSION Sanborn & Rao, et al., PNAS, 2015

  79. LOOP FORMATION BY DIFFUSION Sanborn & Rao, et al., PNAS, 2015

  80. LOOP FORMATION BY DIFFUSION Sanborn & Rao, et al., PNAS, 2015

  81. LOOP FORMATION BY DIFFUSION Sanborn & Rao, et al., PNAS, 2015

  82. DIFFUSION DOES NOT EXPLAIN CONVERGENT RULE Sanborn & Rao, et al., PNAS, 2015

  83. DIFFUSION DOES NOT EXPLAIN CONVERGENT RULE Sanborn & Rao, et al., PNAS, 2015

  84. DIFFUSION DOES NOT EXPLAIN WHY LOOPS TEND NOT TO OVERLAP Sanborn & Rao, et al., PNAS, 2015

  85. DIFFUSION DOES NOT EXPLAIN LACK OF FOCAL CONTACTS BETWEEN CHROMOSOMES Sanborn & Rao, et al., PNAS, 2015

  86. DIFFUSION LEADS TO ENTANGLEMENT Sanborn & Rao, et al., PNAS, 2015

  87. LOOPS AND DOMAINS FORM VIA EXTRUSION Najeeb Tarazi, Adrian Sanborn

  88. LOOPS AND DOMAINS FORM VIA EXTRUSION Najeeb Tarazi, Adrian Sanborn

  89. LOOPS AND DOMAINS FORM VIA EXTRUSION Najeeb Tarazi, Adrian Sanborn

  90. LOOPS AND DOMAINS FORM VIA EXTRUSION Sanborn, Rao et al., PNAS 2015

  91. LOOPS AND DOMAINS FORM VIA EXTRUSION Sanborn, Rao et al., PNAS 2015

  92. EXTRUSION EXPLAINS MANY KEY OBSERVATIONS Sanborn, Rao et al., PNAS 2015

  93. EXTRUSION EXPLAINS MANY KEY OBSERVATIONS Loops at convergent CTCF sites Sanborn, Rao et al., PNAS 2015

  94. EXTRUSION EXPLAINS MANY KEY OBSERVATIONS Loops at convergent CTCF sites Loops don’t overlap Sanborn, Rao et al., PNAS 2015

  95. EXTRUSION EXPLAINS MANY KEY OBSERVATIONS Loops at convergent CTCF sites Loops don’t overlap Loops are intrachromosomal Sanborn, Rao et al., PNAS 2015

  96. EQUATIONS FOR SIMULATING EXTRUSION Polymer backbone Lennard-Jones forces Loop bonds

  97. A DAY IN THE LIFE OF AN EXTRUSION COMPLEX Najeeb Tarazi, Adrian Sanborn

  98. A DAY IN THE LIFE OF AN EXTRUSION COMPLEX Najeeb Tarazi, Adrian Sanborn

  99. A DAY IN THE LIFE OF AN EXTRUSION COMPLEX Najeeb Tarazi, Adrian Sanborn

  100. LOOP EXTRUSION FORMS 
 SPATIALLY SEGREGATED DOMAINS Najeeb Tarazi, Adrian Sanborn

Recommend

4. Molecular dynamics Understanding Molecular Simulation Molecular Simulations Molecular

4. Molecular dynamics Understanding Molecular Simulation Molecular Simulations Molecular

4. Molecular dynamics Understanding Molecular Simulation Molecular Simulations Molecular dynamics : solve equations of motion r 1 r 2 r n Monte Carlo : importance sampling r 1 r 2 r n Understanding Molecular Simulation Molecular

618 views • 38 slides
3. Monte Carlo Simulations Understanding Molecular Simulation Molecular Simulations Molecular

3. Monte Carlo Simulations Understanding Molecular Simulation Molecular Simulations Molecular

3. Monte Carlo Simulations Understanding Molecular Simulation Molecular Simulations Molecular dynamics : solve equations of motion r 1 r 2 r n Monte Carlo : importance sampling r 1 r 2 r n Understanding Molecular Simulation Monte Carlo

1.02k views • 50 slides
2. Thermodynamics Introduction Understanding Molecular Simulation Molecular Simulations

2. Thermodynamics Introduction Understanding Molecular Simulation Molecular Simulations

2. Thermodynamics Introduction Understanding Molecular Simulation Molecular Simulations Molecular dynamics : solve equations of motion r 1 r 2 r n Monte Carlo : importance sampling r 1 r 2 r n Understanding Molecular Simulation How do

1.02k views • 87 slides
Relationship of Rheological Behavior and Molecular Architecture for LDPE Designed for Extrusion

Relationship of Rheological Behavior and Molecular Architecture for LDPE Designed for Extrusion

Relationship of Rheological Behavior and Molecular Architecture for LDPE Designed for Extrusion Coating Bert Nijhof Technical Paper-7603 Introduction LDPE produced commercially for first time in 1939 Process Radical

430 views • 15 slides
2. Thermodynamics Introduction Understanding Molecular Simulation Molecular Simulations

2. Thermodynamics Introduction Understanding Molecular Simulation Molecular Simulations

2. Thermodynamics Introduction Understanding Molecular Simulation Molecular Simulations Molecular dynamics : solve equations of motion r 1 r 2 r n Monte Carlo : importance sampling r 1 r 2 r n Understanding Molecular Simulation Monte

1.19k views • 88 slides
A Winter Short Course on Statistical Mechanics for Molecular Simulations Lecture 2: Molecular

A Winter Short Course on Statistical Mechanics for Molecular Simulations Lecture 2: Molecular

A Winter Short Course on Statistical Mechanics for Molecular Simulations Lecture 2: Molecular Mechanics & Classical Force Fields Yuan-Chung Cheng yuanchung@ntu.edu.tw 2/2/2015 Many materials taken from Prof. A. D. MacKerells

1.16k views • 61 slides
Efficient dynamic closed-loop simulations of flexible manipulators Linearised equations of

Efficient dynamic closed-loop simulations of flexible manipulators Linearised equations of

Efficient dynamic closed-loop simulations of flexible manipulators Linearised equations of motion (for e.g. closed-loop simulations) Superposition of rigid link motion and small elastic deformations Perturbation method

254 views • 24 slides
Introduction Statistical Thermodynamics Monday, January 5, 15 1 Molecular Simulations

Introduction Statistical Thermodynamics Monday, January 5, 15 1 Molecular Simulations

Introduction Statistical Thermodynamics Monday, January 5, 15 1 Molecular Simulations Molecular dynamics: MD solve equations of motion r 1 r 2 r n MC Monte Carlo: importance sampling r 1 r 2 r n 2 Monday, January 5, 15 2 3

1.19k views • 82 slides
Objectives You should be able to ... Loop Invariants Explain the concept of well formed

Objectives You should be able to ... Loop Invariants Explain the concept of well formed

od Introduction Loops Loop Equations Loop Invariants Termination Introduction Loops Loop Equations Loop Invariants Termination Objectives You should be able to ... Loop Invariants Explain the concept of well formed induction. Dr.

579 views • 5 slides
Structural biomathematics: an overview of molecular simulations and protein structure prediction

Structural biomathematics: an overview of molecular simulations and protein structure prediction

A Glance at Structural Biology Molecular Simulations Direct-Coupling Analysis for Prediction of Protein Folding Structural biomathematics: an overview of molecular simulations and protein structure prediction Bernat Anton Bernat Anton

859 views • 43 slides
Self-consistent coupling of molecular theory of solvation with molecular simulations Presented

Self-consistent coupling of molecular theory of solvation with molecular simulations Presented

Self-consistent coupling of molecular theory of solvation with molecular simulations Presented by: CAO Siqin, Jan 7 Solvate with 3D-RISM-KH Bridge between solvation theory and other methods: = + Solvate with 3D-RISM-KH: Andriy Kovalenko and

367 views • 8 slides
of Pure and Alloy Nanoclusters via Molecular Dynamics Simulations NAME: ONG YEE PIN MATRIC NO.:

of Pure and Alloy Nanoclusters via Molecular Dynamics Simulations NAME: ONG YEE PIN MATRIC NO.:

Thermal Properties and Ground-state Structures of Pure and Alloy Nanoclusters via Molecular Dynamics Simulations NAME: ONG YEE PIN MATRIC NO.: P-ZM0007/14(R) ABSTRACT The study of thermal properties of nanoclusters via molecular dynamics

583 views • 55 slides
Lubricated friction at the nanoscale: insights from molecular dynamics simulations and machine

Lubricated friction at the nanoscale: insights from molecular dynamics simulations and machine

Lubricated friction at the nanoscale: insights from molecular dynamics simulations and machine learning Lasse Laurson Aalto University, Finland Collaborators: Wei Chen, Pritam Kumar Jana, Filippo Federici, Martha Zaidan, Adam S. Foster, Mikko

547 views • 18 slides
Substructure from Simulations Can the standard reionization scenario explain the current

Substructure from Simulations Can the standard reionization scenario explain the current

Substructure from Simulations Can the standard reionization scenario explain the current population of satellite galaxies? (How low does galaxy formation go?) James S. Bullock (UC Irvine) Tyler Kelley ( UC Irvine ) ( UC Irvine > Texas

909 views • 45 slides
Efficient Parallelization of Molecular Dynamics Simulations on Hybrid CPU/GPU Supercoputers

Efficient Parallelization of Molecular Dynamics Simulations on Hybrid CPU/GPU Supercoputers

Efficient Parallelization of Molecular Dynamics Simulations on Hybrid CPU/GPU Supercoputers Jaewoon Jung (RIKEN, RIKEN AICS) Yuji Sugita (RIKEN, RIKEN AICS, RIKEN QBiC, RIKEN iTHES) Molecular Dynamics (MD) 1. Energy/forces are described by

605 views • 23 slides
Preventing Premature Conclusions Analysis of Human-In-the-Loop Air Combat Simulations 30 August

Preventing Premature Conclusions Analysis of Human-In-the-Loop Air Combat Simulations 30 August

Preventing Premature Conclusions Analysis of Human-In-the-Loop Air Combat Simulations 30 August 2012 Matthew MacLeod Centre for Operational Research and Analysis Outline The issue Randomness and expectation Issues with small samples

486 views • 24 slides
Uncertainty quantification of Molecular Dynamics Simulations for Crosslinked Polymers Paul

Uncertainty quantification of Molecular Dynamics Simulations for Crosslinked Polymers Paul

Uncertainty quantification of Molecular Dynamics Simulations for Crosslinked Polymers Paul Patrone (IMA / NIST) Andrew Dienstfrey (NIST Boulder) Steve Christensen, Andrea Browning, Sam Tucker (Boeing) Backstory: Macro-economics of materials

390 views • 22 slides
Probing Protein Mechanics with Probing Protein Mechanics with Molecular Dynamics Simulations and

Probing Protein Mechanics with Probing Protein Mechanics with Molecular Dynamics Simulations and

Probing Protein Mechanics with Probing Protein Mechanics with Molecular Dynamics Simulations and Molecular Dynamics Simulations and Single-Molecule Experiments Single-Molecule Experiments PRAC: The Computational Microscope PI: Emad

447 views • 34 slides
Reweighting Techniques for Monte Carlo and Molecular Dynamics Simulations I Yuko OKAMOTO

Reweighting Techniques for Monte Carlo and Molecular Dynamics Simulations I Yuko OKAMOTO

The 13th KIAS Protein Folding Winter School High 1 Resort, Korea January 19-24, 2014 Reweighting Techniques for Monte Carlo and Molecular Dynamics Simulations I Yuko OKAMOTO Department of Physics and Structural Biology

554 views • 39 slides
2007 TAPPI EUROPEAN PLACE Modern Extrusion Coating Die Technology Sam Iuliano Extrusion Dies

2007 TAPPI EUROPEAN PLACE Modern Extrusion Coating Die Technology Sam Iuliano Extrusion Dies

2007 TAPPI EUROPEAN PLACE Modern Extrusion Coating Die Technology Sam Iuliano Extrusion Dies Industries, LLC Performance Needs Precise control of coat weight uniformity Trouble-free coating width variation Ability to reduce edge

606 views • 25 slides
Towards development of easy-to-use molecular diagnostic method for HAT ~ Loop-mediated isothermal

Towards development of easy-to-use molecular diagnostic method for HAT ~ Loop-mediated isothermal

Towards development of easy-to-use molecular diagnostic method for HAT ~ Loop-mediated isothermal amplification of DNA ~ O. M. M. Thekisoe 1 , M. Inoue 1 , J. Ndungu 2 , N. Inoue 1 * 1 OIE Reference Laboratory on Surra National Research Center

310 views • 28 slides
Development of BioBased Packaging Development of BioBased Packaging via Tw in Screw Extrusion

Development of BioBased Packaging Development of BioBased Packaging via Tw in Screw Extrusion

Extrusion Technology Development of BioBased Packaging Development of BioBased Packaging via Tw in Screw Extrusion via Tw in Screw Extrusion Next Generation Bio-Based Chemicals Charlie Martin/Leistritz Ph: 908/685-2333, E-mail:

494 views • 32 slides
PET extrusion coating - taking extrusion coating to a new level Mr. Mikko Peltovuori 10, 7630

PET extrusion coating - taking extrusion coating to a new level Mr. Mikko Peltovuori 10, 7630

PET extrusion coating - taking extrusion coating to a new level Mr. Mikko Peltovuori 10, 7630 PET Extrusion coating Polymer comparison PE vs. PET Equipment Processing Applications 7030 10,1 Mikko Peltovuori 2 Polymer

435 views • 22 slides
Using Q-Chem for molecular simulations at NERSC Evgeny Epifanovsky June 29, 2018 What is

Using Q-Chem for molecular simulations at NERSC Evgeny Epifanovsky June 29, 2018 What is

Using Q-Chem for molecular simulations at NERSC Evgeny Epifanovsky June 29, 2018 What is Q-Chem? Established in 1993, first release in 1997. Software Development platform Q-Chem 3.0 (2006) Supported infrastructure for 4.0 (2012)

734 views • 20 slides

More recommend