EmbryoMaker User's Manual v 1.0
Contents
1. Allows to change the maximum radius of spheres by dragging the mouse with the left button 4 2 2 6 2 Change sphere max and min from terminal This option will change the minimum and maximum values of the node property selected taken into account for setting semitransparent sphere radius for each node All values below the minimum value will have a sphere radius of 0 and all values above the maximal value will have a sphere radius equal to the sphere scale 1 by default The minimum and maximum values will be entered via terminal in the same line separated with a space in the respective order 4 2 2 6 3 Change sphere min with left mouse button This button allows to change the minimum value described above simply dragging the mouse with the left button 4 2 2 6 4 Change sphere max with left mouse button This button allows to change the maximum value described above simply dragging the mouse with the left button 4 2 2 6 5 Change sphere min with middle mouse button This button allows to change the minimum value described above simply dragging the mouse with the middle mouse button this means pressing the scrolling wheel not actually scrolling 4 2 2 6 6 Change sphere max with middle mouse button This button allows to change the maximum value described above simply dragging the mouse with the middle mouse button this means pressing the scrolling wheel not actually scrolling node type cells 4 2 2 6 7 Disable sphere This op2. axis will be displayed 4 2 2 9 As dtotal The total distance a node has moved will be displayed 4 2 2 10 As node index The index within the node matrix will be displayed 4 2 2 11 Amount of regulatory molecule X The variable displayed will be the amount of a certain molecule expressed in each node There will be one of those options for each regulatory molecule described in the system to be simulated it may change in different developmental simulations epithelial springs 4 2 3 What to draw Menu box grid connexions between cells Note that some drawing options will not have a visible effect connexions between nodes if other things are drawn in front most notably one should draw cell contour chose to draw small balls only if one wishes to see the other dravemmtetcemaar contour balls as radius EQD options balls as radius ADD ws small balls Note also that these options activate a specific drawing when no balls chosen and deactivate it when chosen again cylinders only upper balls 4 2 3 1 Epithelial springs Draws the springs between Only lower balls the pair of nodes of the epithelium with green lines ciaal ede Me ed polarization vectors troid 4 2 3 2 Box grid Draws a 3D grid around the embryo a The distance between grid points is proportional to the show displacement of nodes from origin maximal ADD of the nodes in the embryo movement unitary vectors force component repulson adhesion 4 2 3 7 Connexions between ce
3. pairs of nodes with a radius equal to the node property ADD that is the radius on which adhesion can occur When pressing the right button a menu will appear The following pages detail these options in detail 4 1 Principal Menu options Basic View Modifier gt 4 1 1 Basic View Modifier This option shows a submenu with Roe NCE Ties Oe options to modify the view of the model results By default pressing show other node properties gt the left mouse button and moving the mouse would rotate the what to draw gt embryo but other options in this menu allow the mouse to do input output gt different things on the view These options are described in section Editor gt 4 2 1 selection menu gt 4 1 2 Show node mechanical properties This menu allows to display ears Hones ti gt mechanical node properties in three ways through the color of Beep Oily ORONS gt nodes through drawing a series of arrows whose length is nee ene gt proportional to the value of the property only applicable to 1 iteration epithelia and through drawing semitransparent spheres over nodes 100 iterations whose size reflect the value of the property There are also several 11000 iterations options to tune the display of each of the three methods Node 50000 iterations coloring arrows and transparent spheres and independent thus one can display a different node property with each method but not more than one with the same method at once See section 4 2 2
4. this can be installed by running apt get install gnuplot 2 1 2 Building Download the tar file from the website and save it in the place you want to install the software Uncompress the tar file You may do that by opening a terminal going to the directory where the tar file is stored and typing the following command tar xzvf lt EmbryoMaker_directory gt tar gz where lt EmbryoMaker_directory gt stands for the name the downloaded tar file has at that moment While in the terminal enter the lt EmbryoMaker_directory gt and simply run the compile_EmbryoMaker sh script You may need to grant execution permissions to the script first in that case type chmod x compile_EmbryoMaker sh then to run the script type compile_EmbryoMaker sh the following output should be printed in the terminal descending lt path_to_EmbryoMaker_dir gt src core making object files linking cleaning executables installed in bin The executable is named EMaker and is placed in the bin directory 2 2 Mac 2 2 1 Software requirements Xcode MacPorts gcc46 the exact command is sudo port install gcc46 2 2 2 Building Download the EmbryoMaker tar file from the website and save it in the place you want to install the software Uncompress the EmbryoMaker tar file While in the terminal enter the EmbryoMaker directory and simply run the compile_EmbryoMaker_mac sh script Note that if your OS X version is 10 6 y
5. x iterations quit 4 1 3 Show other node properties This menu allows to display non mechanical node properties such as node type gene expression etc This can be displayed in three ways through the color of nodes through drawing a series of arrows whose length is proportional to the value of the property only applicable to epithelia and through drawing semitransparent spheres over nodes whose size reflect the value of the property There are also several options to tune the display of each of the three methods Node coloring arrows and transparent spheres and independent thus one can display a different node property with each method but not more than one with the same method at once 4 2 3 4 1 4 What to draw This option shows a submenu with a list of options to choose which parts of the embryo are shown in the display and how are those shown These options are described in detail in section 5 2 4 4 1 5 Input Output This option shows a submenu with a list of options to save the current state of the embryo into a file or to read previous states from a file See section 4 2 5 4 1 6 Editor This menu includes all the options to edit the developmental system such as adding or deleting nodes or cells and changing their properties or gene expression See section 4 2 6 4 1 7 Selection menu This menu shows different options to select nodes or cells This is useful to simply track nodes or cells over time but also allows to use the e
6. EmbryoMaker User s Manual v 1 0 Miquel Marin Riera Miguel Brun Usan Roland Zimm Tommi V likangas Isaac Salazar Ciudad a Genomics Bioinformatics and Evolution Departament de Genetica i Microbiologia Universitat Autonoma de Barcelona Barcelona Spain gt Evo devo Helsinki community Centre of excellence in computational and experimental developmental biology Institute of Biotechnology University of Helsinki PO Box 56 FIN 00014 Helsinki Finland Index 1 Download Software 2 Installation 2 1 Linux 2 1 1 Software requirements 2 1 2 Building 2 2 Mac 2 2 1 Software requirements 2 2 2 Building 3 Command line execution options 3 1 Example files Basic developmental mechanisms 4 Running EmbryoMaker with its visual interface Linux 4 1 Principal Menu options 4 2 Submenu options 1 Download Software The EmbryoMaker software can be downloaded from http www biocenter helsinki fi salazar software html 2 Installation 2 1 Linux 2 1 1 Software requirements Freeglut libraries http freeglut sourceforge net In Ubuntu this can be installed by running apt get install freeglut3 dev Mesa Openg libraries http www mesa3d org They are normally already installed in most linux distributions gfortran compiler https gcc gnu org wiki GFortran In Ubuntu this can be installed by running apt get install gfortran Gnuplot Optional http www gnuplot info In Ubuntu
7. above but for the apical basal epithelial surface tension 4 2 3 27 Movement module vectors As 4 2 3 19 but the line has a longitude proportional to the amount of movement in the last iteration 4 2 3 28 Do not show show epithelium 4 2 3 29 Do not show show mesenchyme 4 2 3 30 Do not show show extracellular matrix 4 2 4 Input Output Menu save present time save snaps periodically 4 2 4 1 Save present time Change frequency of snapshots Save a present state of the read from file embryo This includes all add label to the name of the output file model parameters including save images automatically the window must be open and uncovered the genetic ones and also all save movie check terminal the window must be open and uncovered node and cell properties When this file is read either from the graphical interface or by calling the simulator with that file in the command line everything is recovered including the iteration number In that sense this file can be used as the initial conditions for other simulator runs The file is saved in a directory within the output directory in the directory where the simulator has been executed The directory and the file have a random name that includes the date when it was run This name is the same than the name of the window The output file is a text file and it can be open by any plain text editor The meaning of the values saved in it are explained in the same file and can b
8. agging the mouse with the left button and is moved in the z axis by dragging with the middle mouse button pressing the scrolling wheel 4 2 8 2 Set left mouse button for x y move When selected the cursor can be displaced in the x y plane whith the left mouse button This is the cursor displacement mode by default 4 2 8 3 Set left mouse button for z move When selected the cursor can be displaced in the z plane whith the left mouse button The user can also alternatively switch between cursor displacements in the x y or z plane 4 2 8 2 or 4 2 8 3 options by pressing the DOWN key in the keyboard 4 2 8 4 Set middle mouse button for z move As in 4 2 8 3 but using the middle mouse button instead of the left mouse button Gene plotting options 4 2 9 1 Temporal plots ON OFF It is set ON by default and each time the button is pressed it switches between the ON and OFF Temporal plots ON OFF options When ON option is set the node properties concerning plot gen vs time in a node concentration of regulatory molecules are stored so as they can be tracked along time and plotted if 4 2 9 2 is chosen These data are not stored each iteration but each time the user runs a number of iterations If OFF option is set the concentrations are not stored however data previously stored are not deleted and the program runs slightly faster When the program is run in the automatic mode see section 3 the OFF option is automaticall
9. al node Note that this option will only be visible for epithelial nodes p GRD PLD VOD p DIF p KFI p PLA 4 2 2 3 with semitransparent spheres Submenu This submenu allows you to select a mechanical node property to be displayed as semitransparent spheres of different radius over each node 4 2 2 4 Color options Submenu This submenu allows to set different options regarding the coloring of nodes 4 2 2 4 1 Change color palette Submenu Allows you to choose between 4 different color palettes 4 2 2 4 2 Change color max and min from terminal This option will change the minimum and maximum values of the node property selected taken into account for coloring each node All values below the minimum value will have the same minimum color depending on the palette and all values above the maximal value will have the same maximum color The minimum and maximum values will be entered via terminal in the same line separated with a space in the respective order 4 2 2 4 3 Change color min with left mouse button change color palette gt This button allows to change the minimum value select color max and min from terminal described above simply dragging the mouse with the iSelect color min with left mouse button left button select color max with left mouse button select color min with middle mouse button 4 2 2 4 4 Change color max with left mouse button leat Color mas avin middla mouse button This button allows to change t
10. as been modified by the Delete the selected cell user and the editor is put to sleep If elli e is run ia pete er oe eure ey ange properties of the selected cell with an input file the embryo encoded in this file Change gene expression in the selected node can be edited and then saved in a different file This Choose a node in which to Paste properties of the selected node latter file can then be used as the initial conditions Paste a property into it gt for other runs of elli e STOP the editor and go back to running mode In most simulations in development as in most studies in developmental biology in general one studies a system e g organ or embryo part from some chosen early developmental stage to some later developmental stage to try to understand how one transforms into the other In practice this often involves trying to understand how a specific spatial distribution of cell types what we call in here an initial developmental pattern transforms into another one what we call in here a final developmental pattern The embryo editor allows the user to precisely describe in the model this initial pattern this is the initial spatial distribution of cells nodes their properties and gene expression from which the development he she wants to study starts Then by using the gene network editor the user can study which gene networks and which regulation of which cell behaviors by those are able to lead development from this initial c
11. bsubmenu listing all node properties The chosen property will be copied from the selected node to the target node 4 2 5 14 STOP the editor and go back to running mode This option deactivates the embryo editor and goes back to running mode selection mode select node by index 4 2 7 Selection menu selection mode cell by index selection mode select node with cursor 4 2 7 1 Selection mode select node by index When selected selection mode select cell with cursor the user should enter in the command line the index es of confirm selection with cursor the node s to be selected When the last selected node has lundo selections been introduced the user has to type 1 to end selection When a node is selected it will be coloured in white or yellow and some of its basic properties such as position or energy will be shown in the terminal The last node selected will always be colored in yellow and will be the one set for using the editor options see section 4 2 5 and the moving options see section 4 2 10 The rest of the selected nodes if 4 2 8 4 2 9 any will be colored in white 4 2 7 2 Selection mode select cell by index As in 4 2 7 1 but in here what the user should enter in the command line are the index es of the cell s to be selected 4 2 7 3 Selection mode select node with cursor This option allows the user to select nodes using the cursor By default the cursor is moved in the x y plane by dragging the mou
12. ditor options section 4 2 6 on them and to plot their gene expression over time using the gene plotting options menu section 4 1 9 4 1 8 Cursor menu This menu includes all options regarding the control of the cursor a tool mainly used to select nodes see Section 4 1 7 or to mark a reference point in space See section 4 2 8 4 1 9 Gene plotting options This menu allows to plot the gene expression of one or several nodes over time using the GNUplot software make sure it s installed in your computer before using this option See section 4 2 9 4 1 10 Move menu This menu allow to move nodes and cells in space in different ways see section 4 2 10 4 1 11 1 iteration Runs the model for 1 iteration After this is chosenThe window will lock while this number of iterations are running in the simulator When these are run the current state of the embryo will be shown in the window and the use will win control on the display again Notice that depending on the number of nodes and the running options this iteration may take more or less time 4 1 12 100 iterations As above but the model is run for 100 iterations 4 1 13 1000 iterations As above but the model is run for 1000 iterations 4 1 14 50000 iterations As above but the model is run for 50000 iterations A prompt indicating the number of nodes the number of iterations and other basic information will appear in the terminal every 1000 iterations 4 1 15 x iterations When t
13. e directly used by the user as an alternative way to change the embryo s State 4 2 4 2 Save snaps periodically By choosing this option the state of the embryo is automatically saved into a different file every 1000 iterations 4 2 4 2 Change frequency of snapshots This options prompts a message in the terminal where the user should introduce the iterations intervals in which snaps are taken 4 2 4 5 Read from file A prompt would arise in the terminal asking the user to introduce the name and address of the file the user wants to read 4 2 4 6 Add label to the name of the output file Adds a label given trough the terminal at the end of the output files saved 4 2 4 5 Save images automatically Snapshots of the system will be taken during simulation time The amount and frequency of snapshots is set automatically 4 2 4 6 Save movie check terminal Same as previous option but you need to specify the amount and frequency of snapshots via terminal 4 2 5 Editor Menu Add basic epithelial cell Embryo editor The options in this submenu allow Add basic mesenchymal cell to edit the embryo Through it the user moves cells Add node to a selected cell Add extracellular node and nodes modify their properties and create new Paste a node from selection nodes and cells or delete existing ones This editor Paste a cell from selection can be used at any moment and simulations can be Delete the selected node resumed after the embryo h
14. ectory this directory is different for every run The output will be saved in the output directory at regular time intervals and for a fixed number of iterations To change that you can do EMaker 0 1 X Y Where X is the duration of each time interval and integer number and Y is how many of those intervals are run and integer number Thus the simulation is run by X Y iterations Running the model automatically without graphical interface from the initial conditions and parameters in a file EMaker lt name of the file gt 1 In this case we can also modify X and Y EMaker lt name of the file gt 1 X Y 3 1 Example files Basic developmental mechanisms EmbryoMaker comes with a set of example files that specify the initial conditions for the basic developmental mechanisms plus a complex developmental mechanism The initial condition files are in the examples directory within the EmbryoMaker directory In order to run them follow the instructions in section 3 4 Running EmbryoMaker with its graphic interface Linux After the program is executed a window will arise displaying an initial condition in 3D This is the embryo organ or embryo part that is being simulated The use can run a number of iterations by choosing specific options in the menu and see how that embryo or organ changes over developmental time The user can also modify how the embryo is viewed and how it is drawn In the default view cylinders are shown as
15. he maximum value described above simply dragging the mouse with the left button 4 2 2 4 5 Change color min with middle mouse button This button allows to change the minimum value described above simply dragging the mouse with the middle mouse button this means pressing the scrolling wheel not actually scrolling 4 2 2 4 6 Change color max with middle mouse button This button allows to change the maximum value described above simply dragging the mouse with the middle mouse button this means pressing the scrolling wheel not actually scrolling change arrow scale with left mouse button select arrow max and min from terminal select arrow min with left mouse button select arrow max with left mouse button select arrow min with middle mouse button select arrow max with middle mouse button disable arrows 4 2 2 5 Arrow options Submenu This submenu allows to set different options regarding the arrow display of nodes properties 4 2 2 5 1 Change arrow scale with left mouse button Allows to change the maximum length of arrows by dragging the mouse with the left button 4 2 2 5 2 Change arrow max and min from terminal This option will change the minimum and maximum values of the node property selected taken into account for setting arrow length for each node All values below the minimum value will have an arrow length of 0 and all values above the maximal value will have an arrow length equal to the arrow scale 1 by defaul
16. his option is chosen a prompt will arise in the termFotat enter the number of iterations he she wants to run zoom pan 4 1 16 Quit Quits the simulator au ire AE Section from minimal x plane viewstrom above Section from maximal x plane view from front Section from minimal y plane Undo sections Section from maximal y plane Toggle Fixed sections when running iterations Section from minimal z plane Section from maximal z plane 4 2 Submenu options 4 2 1 Basic View Modifier Menu 4 2 1 1 Left mouse button Submenu By choosing one of the options the user decides what happens when dragging with the left mouse button 4 2 1 1 1 Rotate The camera roates This is the default 4 2 1 1 2 Zoom Zoom the cammera in an out 4 2 1 1 3 Pan Moving the camera point of rotation 4 2 1 1 4 Section from the Minimal x plane The mouse will section the embryo as it is moved starting from the node with the minimal x position This is very useful to see the interior of the embryo By default all sections will be undone when the simulation resumes i e running some iterations Sections can be kept over time with the see section 4 2 1 6 to set it otherwise 4 2 1 1 5 Section from the Maximal x plane As above but starting from the node with the maximal x position 4 2 1 1 6 Section from the Minimal y plane As above but starting from the node with the minimal y position 4 2 1 1 7 Section from the Maximal y plane As above but starting from the node w
17. ith the maximal y position 4 2 1 1 8 Section from the Minimal z plane As above but starting from the node with the minimal z position 4 2 1 1 9 Section from the Maximal z plane As above but starting from the node with the maximal z position These different directions of sectioning can be combined to section the embryo from different sides 4 2 1 2 Reset to initial view This shows the embryo from the same default view than when the program was started 4 2 1 3 View from above Adjusts the view to be from top from large z values 4 2 1 4 View from front As above but to see from the front 4 2 1 5 Undo sections All sections will be undone with colors eee gt and the whole system will be visible with arrows only epithelia p with transparent spheres p EQD 4 2 1 6 Toggle fixed sections when running color options gt p ADD iterations This allows to switch between keeping arrow options b Biss the sections during simulations time or being sphere options gt TEE undone when some iterations are run By default p REC this option is set to the second case p EST p ERP 4 2 2 Show node mechanical properties Menu p EQS 4 2 2 1 with colors Submenu This submenu allows you to select a mechanical node p HOO property to be displayed as node color fees 4 2 2 2 with arrows only epithelia Submenu This submenu allows you to select a ase mechanical node property to be displayed as arrows of different length over each p cop epitheli
18. lls Draws a lines force component epi surface tension lateral between those nodes from different cells that are in force component epi surface tension apical basal movement module vectors do not show show epithelium do not show show mesenchyme do not show show extracellular matrix physical contact These lines are red between nodes of different epithelial cells and green between apical nodes of the epithelium and mesenchymal nodes 4 2 3 8 Connexion between nodes Draws red lines between the nodes of the same cell 4 2 3 9 Draw cell contour Draws cellular contours by rendering surfaces between neighboring nodes of the same cell using a 3D Delaunay triangulation 4 2 3 10 Draw intercellular contour Complements the previous option by also rendering surfaces between nodes belonging to different cells displaying thus the space occupied by a compact tissue 4 2 3 11 Balls as radius EQD Nodes are draw as balls of radius equal to the EQD node property of each node 4 2 3 12 Balls as radius ADD Nodes are draw as balls of radius equal to the ADD node property of each node 4 2 3 13 Small balls Draws the nodes with very small balls Very useful for the visualization of forces or connections between nodes 4 2 3 14 No balls Doesn t draw the balls Very useful for the visualization of forces or connections between nodes 4 2 3 15 Cylinders Draws the cylinders of epithelial cells When this option is activated the display of ba
19. lls in epithelial nodes is disabled and viceversa 4 2 3 16 Only upper balls Draws only the apical purple side of the epithelium 4 2 3 17 Only lower balls Draws only the basal blue side of the epithelium 4 2 3 18 Display box boundaries Shows the boundaries of the display box Only elements inside this box will be displayed The display box is useful to make sections of the system 4 2 3 19 Polarization vectors Draws a line for the polariztion vector of each cell 4 2 3 20 Centroids Shows the centroids this is average of the positions of the nodes in a cell of each cells by a white ball 4 2 3 21 Fixed nodes Show nodes fixed in space that is with node property p different from 0 see online methods 4 2 3 22 Show displacement of nodes from origin Shows a line from the initial position of the node to its actual position For nodes that arise by growth this initial position is the position at which that node was created 4 2 3 23 Movement unitary vectors Shows a line for each node in the direction in which it moved in the last iteration 4 2 3 24 Force components repulsion and adhesion Shows a line for each node in the direction in of the repulsion and adhesion forces affecting the nodes in the last interation 4 2 3 25 Force components epi surface tension lateral As above but for one of the torsion forces acting between epithelial cylinders 4 2 3 26 Force components epithelial surface tension apical basal As
20. ondition to the final pattern e g later stage of interest FIG The embryo editor can be used to produce any arbitrary distribution of cells and nodes that involves mesenchyma epithelia and or extracellular matrix with any arbitrary distribution of gene expression in it The embryo editor can also be used to explore the effects on development of a number of experiments occurring at any arbitrary time and place during development To do that the user should simply run the model until the time in development where the manipulation occurs then activate the embryo editor make the corresponding manipulations stop the embryo editor and resume the running of the model from that time point The experimental manipulations that can be used are not restricted to moving cells or changing the expression of specific genes in specific cells or cell parts More sophisticated and realistic experiments can also be implemented Bead experiments can be implemented by adding one or several extracellular matrix node in a desired location and setting its properties to mimic those of a bead its radius and mechanical consistency Then in this node the user can by using the embryo editor chose to put specific concentrations of diffusible molecules Physical barrier experiments can similarly be implemented by adding sets of bound extracellular matrix elements Transgenes and other kinds of genetic manipulations can be simulated by choosing and modifying gene networks with
21. ou should run the compile_EmbryoMaker_mac 10 6 sh script instead The following output should be printed in the terminal descending lt path_to_EmbryoMaker_dir gt src core making object files linking cleaning executables installed in bin The executable is named EMaker and is placed on the bin directory This has been tested on OS X 10 6 Snow Leopard compile_EmbryoMaker_mac 10 6 sh should be used and 10 9 Mavericks compile_EmbryoMaker_mac sh should be used it might not work in other versions 3 Command line execution options This section provides a brief description of how to run the program executable and about its several command line options Simplest option Open a terminal and go to the directory where the simulator has been installed Then type Emaker This simply runs the model with its full graphical interface and the default initial conditions and parameter values see section 4 Before starting the graphical interface the program will let you choose between several default initial conditions Running from the initial conditions and parameters in a file EMaker lt name of the file gt Visualizing an output file EMaker lt name of the file gt Running the model automatically without graphical interface with the default initial conditions and parameters EMaker 0 1 Each time interval is a different file and all the files from the same simulation are saved in a directory within the ouput dir
22. se with the left button Pressing the DOWN key will toggle between x y movement and z movement by dragging the mouse with the left button In order to select node approach the cursor to the desired node and press the mouse middle button press the scroll wheel but don t scroll the wheel In case your mouse doesn t have a middle button see section 4 2 7 5 4 2 7 4 Selection mode select cell with cursor As in 4 2 7 3 but in here what is selected is the cell that is closest to the cursor 4 2 7 5 Confirm selection with cursor This option will select the node or cell that is closer to the cursor Note that in order to work you need to select before one of the two selection modes that use the cursor 4 2 7 3 or 4 2 7 4 This option does the same as clicking with the middle button when the selection mode is active 4 2 7 6 Undo selections All selected elements not only the latter one are unselected Cursor menu cursor ON OFF 4 2 8 1 Cursor ON OFF Toggle cursor function It is set set left mouse button for x y move OFF by default When activated the cursor appears in the set left mouse button for z move display window as a red solid ball which can be moved by set middle mouse button for z move the user across the system to select nodes and cells see section 4 2 7 2 Notice that since the cursor appears in a corner of the window it can be necessary to move it to make it visible By default the cursor is moved in the x y plane by dr
23. selected cell It adds a node to the selected cell in the current position of the cursor If no cell has been selected before no node will be added and a complaint text will arise in the terminal If the selected cell is epithelial to nodes a cylinder will be added 4 2 5 4 Add extracellular node An extracellular node is added in the current position of the cursor 4 2 5 5 Paste a node from selection A node identical to the selected node is added in the current position of the cursor As before the user needs to select a node before 4 2 5 6 Paste a cell from selection As above but for a cell 4 2 5 7 Delete the selected node The selected node is deleted 4 2 5 8 Delete the selected cell The selected cell is deleted 4 2 5 9 Change properties of the selected node This option will show an subsubmenu listing all node properties After choosing one a message will appear in the terminal giving the present value of this property in the selected node and asking for the new value Press return after introducing this value 4 2 5 10 Change properties of the selected cell As above but for cell properties 4 2 5 11 Change gene expression in the selected node As above but the node properties changed are the gene expression 4 2 5 12 Choose a node in which to Paste properties of the selected node This choses the node that is closest to the current cursor position as a target node 4 2 5 13 Paste a property into it This option will show an su
24. t The minimum and maximum values will be entered via terminal in the same line separated with a space in the respective order 4 2 2 5 3 Change arrow min with left mouse button This button allows to change the minimum value described above simply dragging the mouse with the left button 4 2 2 5 4 Change arrow max with left mouse button This button allows to change the maximum value described above simply dragging the mouse with the left button 4 2 2 5 5 Change arrow min with middle mouse button This button allows to change the minimum value described above simply dragging the mouse with the middle mouse button this means pressing the scrolling wheel not actually scrolling 4 2 2 5 6 Change arrow max with middle mouse button This button allows to change the maximum value described above simply dragging the mouse with the middle mouse button this means pressing the scrolling wheel not actually scrolling 4 2 2 5 7 Disable arrows This option disables the display of arrows 4 2 2 6 Sphere options Submenu This submenu allows change sphere scale with left mouse button to set different options regarding the semitransparent Select sphere max and min from terminal sphere display of nodes properties select sphere min with left mouse button select sphere max with left mouse button select sphere min with middle mouse button select sphere max with middle mouse button 4 2 2 6 1 Change sphere scale with left mouse button PER E
25. the gene network editor The embryo editor works in similar way than vectorial graphics editors such as illustrator inkscape etc but in 3D and with a simpler and Aaabasic epineiiaicel less sophisticated used interface By moving a Add basic mesenchymal cell cursor in the 3D space the user can chose to move Add node to a selected cell cells or nodes from one position to another chose Add extracellular node where to put a new cell or node or copy a cell or Paste anode from selection node and paste it in a new position So the first Paste a cell from selection thing the user needs to do in the embryo editor is Delete the selected node to activate the cursor by choosing the menu mast aul meats cel option Change properties of the selected node gt Change properties of the selected cell gt _ Change gene expression in the selected node ATTENTION All menu options perform 1S Choose a node in which to Paste properties of the selected node action on the positions where the cursor is Paste a property into it gt see Cursor menu X and Selection menu X STOP the editor and go back to running mode gt gt 4 2 5 1 Add basic epithelial cell An epithelial cell with 14 nodes and an hexagonal shape is added in the position where the cursor is The number of nodes and their position can later be modified by the other options in the menu 4 2 5 2 Add basic mesenchymal cell As above but for an epithelial cell 4 2 5 3 Add node to
26. tion disables the display cell nucleus as blue of semitransparent spheres nodes fixed as yellow as cell cycle 4 2 3 Show other node properties Menu It is exactly the same as as dx the previous menu 4 2 2 except for the node properties you can as dy set in each of the three submenus with colors with arrows and with semitransparent spheres The following descriptions as dtotal as boxes as node index Amount of regulatory molecule 1 doesn t refer to all the submenus and options since they are the same as in the previous menu Instead the node properties that available for display in this menu are described 4 2 3 1 Node type The type of node is displayed This is 1 for apical epithelial nodes 2 for basal epithelial nodes 3 for mesenchymal nodes and 4 for ECM nodes 4 2 2 2 Cell The cell index of the cell the node belongs to is displayed 4 2 2 3 Cell nucleus as blue Nodes specified as nuclei will have a value of 0 the rest will have a value of 1 4 2 2 4 Nodes fixed as yellow Nodes fixed in space p different from 0 see online methods will have a value of 1 the rest a value of 0 4 2 2 5 As cell cycle The value of the cell property P of the cell the node belongs to will be displayed 4 2 2 6 As dx The distance a node has moved in the x axis will be displayed 4 2 2 7 As dy The distance a node has moved in the y axis will be displayed 4 2 2 8 As dz The distance a node has moved in the z
27. u had previously selected a node this will be the one moved and if you had several nodes selected it will be the last one selected If there is none selected the terminal will ask for a node index To stop the mouse movement mode select the Stop movement option in the same menu 4 2 10 3 Move cell from terminal This option allows to move a certain cell to a set of coordinates that have to be entered by the terminal If you had previously selected a cell this will be the one moved and if you had several cell selected it will be the last one selected If there is none selected the terminal will ask for a cell index Next it will ask for the new desired coordinates for the cell centroid that will be entered through the terminal sequentially If 1 is typed in any of the coordinates that one will be kept as the original value 4 2 10 4 Move cell with left mouse button This option allows to move a certain cell by dragging the mouse with the left button If you had previously selected a cell this will be the one moved and if you had several cell selected it will be the last one selected If there is none selected the terminal will ask for a cell index To stop the mouse movement mode select the Stop movement option in the same menu Enjoy
28. y chosen 4 2 9 2 Plot gen vs time in a node It plots in a new window the concentration of different regulatory molecules in different nodes along time using Gnuplot When selected the user should enter in the command line the nodes and genes to be plotted The resulting plot will display the concentrations of all chosen genes in all chosen nodes In order to avoid overloaded plots the number of nodes and genes that can be selected are limited to 10 When this option is set and there exist one or more previously selectd node s the user will only have to choose the regulatory molecule s move node from terminal move node with left mouse button 4 2 10 1 Move node from terminal This option allows to Move cell from terminal move a certain node to a set of coordinates that have to be move cell with left mouse button entered by the terminal If you had previously selected anode Stop movement for cursor movement this will be the one moved and if you had several nodes selected it will be the last one selected If there is none selected the terminal will ask for a node index Next it will ask for the new desired coordinates for the node that will be entered through the terminal sequentially If 1 is typed in any of the coordinates that one will be kept as the original value 4 2 10 Move menu 4 2 10 2 Move node with left mouse button This option allows to move a certain node by dragging the mouse with the left button If yo
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