Team:Heidelberg/Notebook modeling
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- | = | + | = Notebook HEARTBEAT = |
Welcome to the notebook of the HEARTBEAT (Heidelberg Artificial Transcription Factor Binding Sites Assembly and Engineering Tool) project. This notebook comprises the work on three sublanes: HEARTBEAT database (DB), HEARTBEAT graphical user interface (GUI) and HEARTBEAT fuzzy modeling (FN) as well as some additional work on logo as well as wiki design. Have fun! | Welcome to the notebook of the HEARTBEAT (Heidelberg Artificial Transcription Factor Binding Sites Assembly and Engineering Tool) project. This notebook comprises the work on three sublanes: HEARTBEAT database (DB), HEARTBEAT graphical user interface (GUI) and HEARTBEAT fuzzy modeling (FN) as well as some additional work on logo as well as wiki design. Have fun! | ||
- | |||
=='''Contents'''== | =='''Contents'''== | ||
+ | * <span style="font-size:5mm;">[[Team:Heidelberg/Notebook_modeling#July| July]]</span> | ||
- | * August | + | * <span style="font-size:5mm;">[[Team:Heidelberg/Notebook_modeling#August| August]]</span> |
- | + | ||
- | + | ||
- | + | ||
- | + | ||
+ | * <span style="font-size:5mm;">[[Team:Heidelberg/Notebook_modeling#September| September]]</span> | ||
+ | * <span style="font-size:5mm;">[[Team:Heidelberg/Notebook_modeling#October| October]]</span> | ||
== July == | == July == | ||
Line 33: | Line 31: | ||
* aim: create database until end of August | * aim: create database until end of August | ||
- | == | + | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] |
- | {| class="wikitable centered" border="2" rules="rows" width=" | + | |
+ | == August == | ||
+ | {| class="wikitable centered" border="2" rules="rows" width="650px" style="border-color:white;" | ||
|- | |- | ||
- | ! Week | + | ! Week !! colspan="7" |Days |
|- | |- | ||
- | |style="text-align:center"| | + | |style="text-align:center"| |
- | |style="text-align:center"| | + | |style="text-align:center"| Mon |
- | |style="text-align:center"| | + | |style="text-align:center"| Tue |
- | |style="text-align:center"| | + | |style="text-align:center"| Wed |
- | |style="text-align:center"| | + | |style="text-align:center"| Thu |
- | |style="text-align:center"| | + | |style="text-align:center"| Fri |
- | |style="text-align:center"| | + | |style="text-align:center"| Sat |
- | |style="text-align:center"| | + | |style="text-align:center"| Sun |
|- | |- | ||
- | |style="text-align:center"| | + | |style="text-align:center"| 31 |
|style="text-align:center"| - | |style="text-align:center"| - | ||
|style="text-align:center"| - | |style="text-align:center"| - | ||
- | |||
|style="text-align:center"| - | |style="text-align:center"| - | ||
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|style="text-align:center"| - | |style="text-align:center"| - | ||
|style="text-align:center"| - | |style="text-align:center"| - | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-1-2009|1]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-2-2009|2]] | ||
+ | |- | ||
+ | |style="text-align:center"| 32 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-3-2009|3]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-4-2009|4]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-5-2009|5]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-6-2009|6]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-7-2009|7]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-8-2009|8]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-9-2009|9]] | ||
+ | |- | ||
+ | |style="text-align:center"| 33 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-10-2009|10]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-11-2009|11]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-12-2009|12]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-13-2009|13]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-14-2009|14]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-15-2009|15]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-16-2009|16]] | ||
|- | |- | ||
|style="text-align:center"| 34 | |style="text-align:center"| 34 | ||
- | |style="text-align:center"| [[Team:Heidelberg/ | + | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-17-2009|17]] |
- | |style="text-align:center"| [[Team:Heidelberg/ | + | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-18-2009|18]] |
- | |style="text-align:center"| [[Team:Heidelberg/ | + | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-19-2009|19]] |
- | |style="text-align:center"| [[Team:Heidelberg/ | + | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-20-2009|20]] |
- | |style="text-align:center"| [[Team:Heidelberg/ | + | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-21-2009|21]] |
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-22-2009|22]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-23-2009|23]] | ||
+ | |- | ||
+ | |style="text-align:center"| 35 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-24-2009|24]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-25-2009|25]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-26-2009|26]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-27-2009|27]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-28-2009|28]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-29-2009|29]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-30-2009|30]] | ||
+ | |- | ||
+ | |style="text-align:center"| 36 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#8-31-2009|31]] | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| - | ||
|style="text-align:center"| - | |style="text-align:center"| - | ||
|style="text-align:center"| - | |style="text-align:center"| - | ||
|} | |} | ||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
=== 8-3-2009 === | === 8-3-2009 === | ||
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* Start working with MySQL | * Start working with MySQL | ||
* request UNIX/HUSAR/HPC access at DKFZ (Nao) | * request UNIX/HUSAR/HPC access at DKFZ (Nao) | ||
- | * first contact with several databases: EmsEMBL, Compara, cisRED, DoOP, TiProD, contra | + | * first contact with several databases: EmsEMBL, Compara, cisRED, DoOP, TiProD, contra |
=== 8-6-2009 === | === 8-6-2009 === | ||
Line 127: | Line 164: | ||
* installation of R, R editor and perl editor | * installation of R, R editor and perl editor | ||
* further configuration of our internal server / mediawiki | * further configuration of our internal server / mediawiki | ||
+ | * writing first perl program - "Hi there" | ||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
=== 8-10-2009 === | === 8-10-2009 === | ||
Line 145: | Line 185: | ||
*** '''idea 1''': ''error checking'' of affinity: compare expectation to experimental results and figure out where the error is hiding | *** '''idea 1''': ''error checking'' of affinity: compare expectation to experimental results and figure out where the error is hiding | ||
*** '''idea 2''': ''create&visualize fancy and fuzzy data from ''in silico'' simulation | *** '''idea 2''': ''create&visualize fancy and fuzzy data from ''in silico'' simulation | ||
- | ** combine: promoter, output and graphic representation | + | ** combine: promoter, output and graphic representation |
** next meeting with Marti: end of next week. | ** next meeting with Marti: end of next week. | ||
Line 160: | Line 200: | ||
* trying out some DoOP queries | * trying out some DoOP queries | ||
- | * download fasta sequences from UCSC gene browser | + | * download fasta sequences from UCSC gene browser |
* mapping of NCBI Entrez Gene IDs with RefSeq IDs | * mapping of NCBI Entrez Gene IDs with RefSeq IDs | ||
* configure perl working environment on Windows XP | * configure perl working environment on Windows XP | ||
- | * contact Endre Sebestyen concerning the perl module Bio-DoOP-DoOP | + | * contact Endre Sebestyen concerning the perl module Bio-DoOP-DoOP |
=== 8-14-2009 === | === 8-14-2009 === | ||
+ | |||
+ | * parse UCSC fasta sequences according to our selection | ||
+ | * write parsed sequences into multifasta format | ||
* start PromoterSweep Analysis over Weekend | * start PromoterSweep Analysis over Weekend | ||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
=== 8-18-2009 === | === 8-18-2009 === | ||
Line 181: | Line 226: | ||
** MAY contain: position, heartbeat, prediction, assembly, eukaryotes | ** MAY contain: position, heartbeat, prediction, assembly, eukaryotes | ||
** and still more keywords to come | ** and still more keywords to come | ||
+ | *establishing local@host access to mysql | ||
=== 8-19-2009 === | === 8-19-2009 === | ||
- | * parse Promotersweep xml file into tab-separated text file | + | * parse Promotersweep xml file into tab-separated text file |
** the text file should contain: RefSeq ID, TF name, TFBS position, TF motif sequence, TFBS Quality, TSS, Entrez ID, EnsEMBL ID, further gene description. | ** the text file should contain: RefSeq ID, TF name, TFBS position, TF motif sequence, TFBS Quality, TSS, Entrez ID, EnsEMBL ID, further gene description. | ||
** this provided us with several programming problems concerning working with multiple arrays, hashes and their combinations (arrays of hashes, hashes of hashes, etc.) thus | ** this provided us with several programming problems concerning working with multiple arrays, hashes and their combinations (arrays of hashes, hashes of hashes, etc.) thus | ||
* studying structure and basic concepts of hash & key | * studying structure and basic concepts of hash & key | ||
+ | *including parsed data into mysql database | ||
+ | |||
+ | === 8-20-2009 === | ||
+ | * pre-decision for our table-structure | ||
+ | ** Table: Main_Info | ||
+ | *** RefSeq ID, TF, TF motif start & end position, TFBS motif score, TFBS quality, TSS database info | ||
+ | ** Table: Gene_Info | ||
+ | *** Ensembl_ID, Gene Symbol, Gene Description. | ||
+ | ** we go for the RefSeq ID to be the '''key''' connecting these two tables. | ||
+ | |||
+ | === 8-21-2009 === | ||
+ | |||
+ | * update script for parsing the Promotersweep output files due to unexpected errors | ||
+ | * we forgot to include "weak" as a category for the TFBS quality - added! | ||
+ | * PromoterSweep result contains information about TSS derived from different promoter databases. On which should we rely, if they differ from each other? | ||
+ | ** We set our highest priority to DoOP database since they show a good accordance within the RefseqID results when compared to other databases (e.g. DBTSS). | ||
+ | |||
+ | * order [http://www.mathworks.com/| Matlab] iGEM licence | ||
+ | |||
+ | * search for a tool to use MySQL in R programming environment | ||
+ | * wiki: write an short article about the German Cancer Research Center ([[Team:Heidelberg/Team_Scientific_Environment|DKFZ]]) | ||
+ | |||
+ | * Meeting with Anna-Lena: once we established our database... then | ||
+ | ** two strategies: | ||
+ | *** manually select interesting transcription factors and analyse them using database queries | ||
+ | *** plot histograms of TFBS occurance within the target promoter sequence (TSS - 1000bp upstream) for each TF and make systematic analysis | ||
+ | ** we go for both! | ||
+ | ** idea for the future: we can analyze combinatorial appearance of distinct TF pairs | ||
+ | |||
+ | * We have a name for our database - we call it - | ||
+ | |||
+ | |||
+ | - wait for it - | ||
+ | |||
+ | |||
+ | '''HEARTBEAT''' database ('''''He'''idelberg '''Ar'''tificial '''T'''ranscription Factor '''B'''inding Site '''E'''ngineering and '''A'''ssembly '''T'''ool) | ||
+ | <br><br><br> | ||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | === 8-24-2009 === | ||
+ | |||
+ | * Meeting with Marti: defining output modeling strategies | ||
+ | ** "exclusive promoters" | ||
+ | *** a model for predicting the behaviour of activation of one, two, three... promoters at the same time. | ||
+ | *** the potential of this model lies in the possibility to model single as well as many pathways in combination and even check for synergistic effects | ||
+ | *** modeling logic: quantitative '''ODE''' VS. quantitative & qualitative '''fuzzy logic''' | ||
+ | ** "error checking" | ||
+ | *** what to capture/measure: affinity of transcription factor binding to DNA | ||
+ | **** calculate score / reliabilty | ||
+ | **** phenotypic measurement | ||
+ | *** if we have time in the end: model/experiment optimization by wetlab-drylab-rounds (GRAFIK) | ||
+ | *** if we do not have much time: figure out where is catch | ||
+ | ** modeling layers & final visualization | ||
+ | *** (i) capture affinity - (ii) model gene expression - (iii) pathway activity - (iv) fancy visualization (Mathworks Simulink?) | ||
+ | *** plot: time course, dynamic affinity | ||
+ | *** keep in mind the possible high amount of False Positives using promoter search/analysis | ||
+ | |||
+ | === 8-25-2009 === | ||
+ | * official Team Meeting also with Mr. Kai Ludwig (LANGE + PFLANZ) as guest for Logo / Title Claim discussion | ||
+ | |||
+ | * so far we have 1753 promoter sequences analyzed by PromoterSweep! | ||
+ | |||
+ | * Meeting with Daniela (Nao): ''Cell Profiler'' for capturing biological images & data analysis based on MATLAB | ||
+ | |||
+ | * working with R module '''RMySQL''' for using the pipeline between R and MySQL | ||
+ | * create a list of useful RMySQL commands | ||
+ | |||
+ | === 8-26-2009 === | ||
+ | * '''Workflow for plotting histogram''' - workflow (SOURCE CODE/S?) | ||
+ | ** make MySQL query using R | ||
+ | ** make list of TFs, avoid duplicates using perl | ||
+ | ** pick up each TF (perl/R) and plot histogram (R) | ||
+ | |||
+ | * create MySQL command list including combinatorial queries | ||
+ | |||
+ | === 8-27-2009 === | ||
+ | |||
+ | * check HEARTBEAT DB for duplicate entries | ||
+ | * how should we plot the histogram? | ||
+ | ** (a) histogram - how "wide" should be each bin? 100bp? 50bp? 20bp? | ||
+ | ** (b) plot probability density | ||
+ | * study Transfac PWM (position weight matrices) for | ||
+ | ** difference in consensus sequences (also ask Anna-Lena) | ||
+ | ** different PWM types (vertebrates, plant, insect, fungi, bacteria, nematodes...) | ||
+ | ** positive control: when histograms are generated and plotted, check distribution of Sp1 | ||
+ | |||
+ | * so far we have 3640 promoter sequences "sweeped"! | ||
+ | |||
+ | *access from R to mysql at the local@host server established | ||
+ | |||
+ | === 8-28-2009 === | ||
+ | * dealing with perl - introduce transition of variables between perl and R | ||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | === 8-31-2009 === | ||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | == September == | ||
+ | {| class="wikitable centered" border="2" rules="rows" width="650px" style="border-color:white;" | ||
+ | |- | ||
+ | ! Week !! colspan="7" |Days | ||
+ | |- | ||
+ | |style="text-align:center"| | ||
+ | |style="text-align:center"| Mon | ||
+ | |style="text-align:center"| Tue | ||
+ | |style="text-align:center"| Wed | ||
+ | |style="text-align:center"| Thu | ||
+ | |style="text-align:center"| Fri | ||
+ | |style="text-align:center"| Sat | ||
+ | |style="text-align:center"| Sun | ||
+ | |- | ||
+ | |style="text-align:center"| 36 | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-1-2009|1]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-2-2009|2]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-3-2009|3]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-4-2009|4]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-5-2009|5]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-6-2009|6]] | ||
+ | |- | ||
+ | |style="text-align:center"| 37 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-7-2009|7]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-8-2009|8]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-9-2009|9]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-10-2009|10]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-11-2009|11]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-12-2009|12]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-13-2009|13]] | ||
+ | |- | ||
+ | |style="text-align:center"| 38 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-14-2009|14]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-15-2009|15]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-16-2009|16]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-17-2009|17]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-18-2009|18]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-19-2009|19]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-20-2009|20]] | ||
+ | |- | ||
+ | |style="text-align:center"| 39 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-21-2009|21]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-22-2009|22]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-23-2009|23]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-24-2009|24]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-25-2009|25]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-26-2009|26]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-27-2009|27]] | ||
+ | |- | ||
+ | |style="text-align:center"| 40 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-28-2009|28]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-29-2009|29]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#9-30-2009|30]] | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| - | ||
+ | |} | ||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | === 9-1-2009 === | ||
+ | * derive transcription factor data using R and MySQL | ||
+ | * plot HEARTBEAT TF hit distribution as histograms & density functions for different PWM subsets (all, vertebrates only, single matrices and joined TFs) | ||
+ | *further completion of the database | ||
+ | |||
+ | === 9-2-2009 === | ||
+ | * discussion on how to make statistical studies on our gained distributions | ||
+ | ** ideas: define maximum and variance -> Nao | ||
+ | * look for motif sequences -> Tim | ||
+ | |||
+ | * we have 4476 sequences analysed by Promotersweep so far! | ||
+ | ** but we are expecting 4700 sequences - check missing ones! | ||
+ | |||
+ | === 9-3-2009 === | ||
+ | * internal team meeting: Tim, Lars, Stephen, Nao | ||
+ | ** select especially interesting TFs | ||
+ | *** criteria: (a) good hits in our distributions; (b) easy experimental handling | ||
+ | *** we go for '''HIF''', '''SREBP''' and '''VDR''' to analyse and make synthetic promoter design | ||
+ | * Transfac PWM: there are some annotaion inconveniences of some matrices | ||
+ | * which "spacer" sequences should we use in order to generate TFBS free sequece parts | ||
+ | |||
+ | * rational design of synthetic promoters | ||
+ | ** Tim: SREBP, Nao: VDR | ||
+ | ** both go for a total number of 10 sequences | ||
+ | ** strategies: | ||
+ | *** single TFs: search for density maxima | ||
+ | *** check combinatorial appearance and design promoter sequences with multiple binding TFs | ||
+ | ** use spacer sequences generated by Lars and check for TFBS using Transfac | ||
+ | ** sequence length: max. 1000bp | ||
+ | |||
+ | * back-up idea: if synthesis does not work for a long (~1000bp) sequence then try to work out a protocol for a two-step promoter synthesis combining one empty (TFBS free) sequence with another which consists of many TF and activator binding sites. | ||
+ | |||
+ | === 9-4-2009 === | ||
+ | * work with Transfac PWM: structure, description, and using consensus sequence | ||
+ | * write script to get the ID's and frequencies for all co-occuring TFBS of VDR and SREBP | ||
+ | * write script for generating consensus sequence based on Transfac PWM and replacing ambiguity code with A, C, G or T <pre>Getconsensus.pl, MakeConsensus.pl</pre> | ||
+ | |||
+ | * Wiki Meeting (Nao) | ||
+ | ** Logo choice & modification | ||
+ | ** choose header pics | ||
+ | ** navigation layout | ||
+ | ** develop a catchy, cool homepage | ||
+ | |||
+ | === 9-5-2009 === | ||
+ | * Meeting with Tim, design synthetic promoter sequences | ||
+ | * check spacer sequence (200bp) for TFBS: one TFBS found; remove it by cutting and shortening the sequence to 190bp) | ||
+ | * Kid3 is a repressor! | ||
+ | |||
+ | === 9-6-2009 === | ||
+ | * design more synthetic promoter sequences by manual iteration process which consists of (i) TFBS check and (ii) TFBS removal & filling up random sequence | ||
+ | |||
+ | * aim: creation of an automatic designing tool for synthetic promoters which include sequence design, transfac search as well as filling the sequence up with spacer sequences. | ||
+ | |||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | === 9-7-2009 === | ||
+ | * check designed sequences for restriction sites <pre>CheckRestrictionsites.pl</pre> | ||
+ | * finish creating sequences | ||
+ | * consider CMV core promoter into the calculation of the relative position of TFBS to the TSS | ||
+ | * create sequences for negative control | ||
+ | ** pure TFBS free sequence | ||
+ | ** sequences with TFBS at minima of the density function | ||
+ | * checking for all sequences for further binding sites with the Transfac match tool | ||
+ | |||
+ | === 9-8-2009 === | ||
+ | * check restriction sites for reverse complementary strand | ||
+ | * add flanking sites with restriction sites and spacer nucleotides to our designed sequences | ||
+ | * is there any possibility to automatize Transfac queries? | ||
+ | * work with combined / joined MySQL query structures | ||
+ | * or solve this process by simply writing new temporary tables? | ||
+ | |||
+ | * workflow summary (short) for manual designing of a synthetic promoter: | ||
+ | ** (A) use random sequence | ||
+ | ** (B) check TF-matrices | ||
+ | ** (C) validate TFs (mouse? human? repressor?) | ||
+ | ** (D) check Transfac and restriction sites | ||
+ | |||
+ | * Phone conference with Kai Ludwig, Logo & Web Design (Nao) | ||
+ | |||
+ | * official Team Meeting | ||
+ | |||
+ | * wiki closure on Oct 21st! | ||
+ | |||
+ | === 9-9-2009 === | ||
+ | |||
+ | * modify synthetic promoter sequences to be ready for ordering | ||
+ | * Sweep more promoter sequences using Promotersweep | ||
+ | * start Modeling | ||
+ | * revise and improve HEARTBEAT | ||
+ | * discuss differences between PWMs | ||
+ | |||
+ | === 9-10-2009 === | ||
+ | * still modifying synthetic sequences to be ready for shipping | ||
+ | * we have altogether 25 designed promoter sequences! | ||
+ | |||
+ | === 9-11-2009 === | ||
+ | * Software Meeting (Stephen, Tim, Nao) | ||
+ | ** compartibility with mediawiki: HTML, perl, php, R, java? | ||
+ | ** GUI design | ||
+ | *** simple interface: single TF, auxiliary TFs, #TFBS, sequence length | ||
+ | *** "interactive": multiple TF, choosing auxiliary TFs, additional information (see [[Team:Heidelberg/Eukaryopedia|Eukaryopedia]]), density function plot & histogram | ||
+ | *** "hyper-interactive" step-by-step design & creation | ||
+ | |||
+ | * Modeling Meeting with Marti and Anna-Lena (Tim, Nao) | ||
+ | ** aim: fancy visualization to show expectation & prediction providing pathway insights | ||
+ | ** TODO/QUESTIONS | ||
+ | *** what is the stimulus? collect possible inputs! | ||
+ | *** measurable outcome: experiments & pathways | ||
+ | *** quality of synthetic sequence: error checking | ||
+ | **** we need to define the '''quality''' of our sequences | ||
+ | ** LEVELS of modeling | ||
+ | *** (1) DNA (2) expression/transcriptional activity (3) output | ||
+ | *** each with corresponding measurement | ||
+ | |||
+ | * general modeling scheme: input - "What we are affecting" - possible outcomes | ||
+ | * how? We use fuzzy logic | ||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | === 9-14-2009 === | ||
+ | * collect input for inducing the system (e.g. p53: CPT, Pifithrin-alpha; NFkB: TNF-alpha etc.) | ||
+ | * phone conference with Kai Ludwig | ||
+ | * learn how to include Perl code into html code | ||
+ | ** learn how to use embperl | ||
+ | ** configure apache2 server such that embperl can be interpreted | ||
+ | ** try to make offline use of embperl working | ||
+ | *try to find nice html editor for ubuntu - (seamonkey, Amaya) | ||
+ | |||
+ | === 9-15-2009 === | ||
+ | * create network picture for meeting tomorrow | ||
+ | * Logo discussion | ||
+ | * Read paper: ''Fuzzy Logic Modeling of Signaling Networks'' (Aldridge 2009) | ||
+ | * learn data management of virtual server | ||
+ | * get an overview about the apache2 file and security system | ||
+ | |||
+ | === 9-16-2009 === | ||
+ | * Modeling Meeting with Marti (Douaa, Tim, Nao) | ||
+ | ** update on available drugs/sequences | ||
+ | ** decide what to model: (A) error checking, and (B) differential expression? | ||
+ | ** use natural promoters to build up model for prediction of activity of synthetic promoters | ||
+ | ** Discussion of TF score | ||
+ | *** Transfac sequence alignment score | ||
+ | *** promotersweep binding site quality | ||
+ | *** relative position to TSS: How? | ||
+ | **** (A) peak width & amplitude, (B) distance to maximal peak & position, (C) number of PEAK, (D) "sliding window" and calculate area under curve, (E) #TFBS (also for comparison of different synthetic promoters) | ||
+ | *** biophysical affinity using TRAP | ||
+ | ** first model: build up either on CMV or on JeT | ||
+ | ** potential: integrate many stimuli -> find out crosstalks of pathways? | ||
+ | |||
+ | * TODO (meeting) | ||
+ | ** collect data | ||
+ | ** define WHAT we want to model | ||
+ | ** summarize available sequences | ||
+ | ** try to formulate IF ... THEN "sentences" | ||
+ | ** check MATLAB & MATLAB Fuzzy Logic Toolbox availability | ||
+ | |||
+ | === 9-17-2009 === | ||
+ | * internal Team Meeting | ||
+ | * find error.log files on the server and learn how to use it | ||
+ | |||
+ | === 9-18-2009 === | ||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | === 9-20-2009 === | ||
+ | * learn how to use tag language of embperl | ||
+ | ** learn how to write loops with embperl | ||
+ | ** access of input variables in embperl -- using the %fdat hash | ||
+ | |||
+ | === 9-21-2009 === | ||
+ | * struggling with how to use R from embperl | ||
+ | |||
+ | === 9-22-2009 === | ||
+ | * Wiki Meeting (Dani, Cori, Nao) | ||
+ | ** install image processing tool | ||
+ | ** design wiki, brainstorming for possible navigation bars | ||
+ | * Wiki Phone Meeting with Kai Ludwig (Nao) | ||
+ | ** design header & presentation-master as well as team shirts | ||
+ | |||
+ | * Seminar: '''Martijn Luijsterburg''' (Karolinska Institute) - ''Heterochromatin Protein 1 is involved in the DNA damage response''. Host: Thomas Höfer, Bioquant | ||
+ | |||
+ | === 9-23-2009 === | ||
+ | * Modeling Meeting with Marti, Anna-Lena (Tim, Nao) | ||
+ | ** contact database group (TP3) | ||
+ | ** statistics: characterizing peaks | ||
+ | *** we go for area under the curve and affinity. optionally we can choose Transfac sequence score and peak height & width | ||
+ | ** strategy to convince the wetlab people from the importance of modeling during the meeting on upcoming friday. | ||
+ | ** MATLAB license? | ||
+ | ** logical gates: try to start creating model topology after Friday | ||
+ | |||
+ | * Presentation: '''Marti Bernado Faura''' (Bioquant, University of Heidelberg): ''Data-driven Fuzzy Logic modeling of Programmed Cell Death'' | ||
+ | ** intro into fuzzy logic | ||
+ | ** system development & work flow of fuzzy logic | ||
+ | ** fuzzy inference & model prediction | ||
+ | ** model types: MISO / MIMO | ||
+ | |||
+ | * Wrap-up meeting: Team HEARTBEAT (Tim, Nao) | ||
+ | ** split up computational work into three tracks: HEARTBEAT DB, HEARTBEAT GUI and modeling | ||
+ | *** database: documentation (until Oct 18), peak characterization, calculate absolute density function | ||
+ | *** GUI: based on ''embperl'', design according to our new wiki | ||
+ | *** modeling: MATLAB license, collect sequences & input data, develop network model, include pathways | ||
+ | |||
+ | * literature work | ||
+ | |||
+ | === 9-24-2009 === | ||
+ | * prepare slides for meeting tomorrow | ||
+ | * pathway search: TNF-alpha/NFkB, VDR, SREBP and crosstalks. NFkB has a lot of pathway crosstalks, while SREBP and VDR show a interesting connection. Upon induction, SREBP activates VDR. | ||
+ | |||
+ | === 9-25-2009 === | ||
+ | * Team Meeting (Wetlab, Nao) | ||
+ | ** short progress report of all of us | ||
+ | ** modeling: discussing scheme, modeling elements and strategies | ||
+ | |||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | === 9-28-2009 === | ||
+ | * Wiki Phone Meeting with Kai Ludwig (Nao) | ||
+ | |||
+ | === 9-29-2009 === | ||
+ | * designed synthetic promoters (HB_0001 - HB_0025) will be joined to CMV core promoter since JeT core promoter contains a Sp1 site in it. All other sequences (random synthesized, e.g.) are coupled with JeT core promoter. | ||
+ | * literature studies on combinatorial ''cis''-regulation as well as on modelig of the lambda-switch | ||
+ | * prepare slides for the next modeling meeting | ||
+ | |||
+ | === 9-30-2009 === | ||
+ | * Wiki Meeting (Dani, Nao) | ||
+ | * MATLAB license order (Jens) | ||
+ | * postpone Yara meeting (Wetlab, Tim) | ||
+ | |||
+ | * got sequences from Lars | ||
+ | * got qRT-PCR setup from Chenchen | ||
+ | |||
+ | * Modeling Meeting with Marti & Anna-Lena (Tim, Nao) | ||
+ | ** still need to collect FACS and microscopy results | ||
+ | ** discuss our network prediction model using TNF-alpha as an example | ||
+ | ** maybe we can use the lambda switch paper as a good starting point for our modeling | ||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | == October == | ||
+ | {| class="wikitable centered" border="2" rules="rows" width="650px" style="border-color:white;" | ||
+ | |- | ||
+ | ! Week !! colspan="7" |Days | ||
+ | |- | ||
+ | |style="text-align:center"| | ||
+ | |style="text-align:center"| Mon | ||
+ | |style="text-align:center"| Tue | ||
+ | |style="text-align:center"| Wed | ||
+ | |style="text-align:center"| Thu | ||
+ | |style="text-align:center"| Fri | ||
+ | |style="text-align:center"| Sat | ||
+ | |style="text-align:center"| Sun | ||
+ | |- | ||
+ | |style="text-align:center"| 40 | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| - | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-1-2009|1]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-2-2009|2]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-3-2009|3]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-4-2009|4]] | ||
+ | |- | ||
+ | |style="text-align:center"| 41 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-5-2009|5]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-6-2009|6]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-7-2009|7]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-8-2009|8]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-9-2009|9]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-10-2009|10]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-11-2009|11]] | ||
+ | |- | ||
+ | |style="text-align:center"| 42 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-12-2009|12]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-13-2009|13]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-14-2009|14]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-15-2009|15]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-16-2009|16]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-17-2009|17]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-18-2009|18]] | ||
+ | |- | ||
+ | |style="text-align:center"| 43 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-19-2009|19]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-20-2009|20]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-21-2009|21]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-22-2009|22]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-23-2009|23]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-24-2009|24]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-25-2009|25]] | ||
+ | |- | ||
+ | |style="text-align:center"| 44 | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-26-2009|26]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-27-2009|27]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-28-2009|28]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-29-2009|29]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-30-2009|30]] | ||
+ | |style="text-align:center"| [[Team:Heidelberg/Notebook_modeling#10-31-2009|31]] | ||
+ | |style="text-align:center"| - | ||
+ | |} | ||
+ | |||
+ | === 10-1-2009 === | ||
+ | * Wiki & Presentation Meeting with Dani (Nao) | ||
+ | |||
+ | === 10-2-2009 === | ||
+ | * some wiki work | ||
+ | |||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
+ | |||
+ | === 10-5-2009 === | ||
- | == | + | === 10-6-2009 === |
- | * | + | * Internal Team Meeting |
- | * | + | ** check out number and measurement plans of randomly assembled synthetic promoters (5x NFkB, 5x p53, 2x pPARg, 2x SREBP) |
- | * | + | |
- | + | * Wiki Meeting (Corinna, Daniela, Nao) | |
+ | ** discuss design of the top page and possible features | ||
+ | ** try out CSS design | ||
- | * | + | === 10-7-2009 === |
+ | * Wiki Design (Nao) | ||
+ | * Wiki Phone Meeting with Kai Ludwig (Nao) | ||
- | + | * MATLAB has arrived! | |
+ | * literature work | ||
- | * | + | * Wetlab Meeting: progress report on measurement of random assembled synthetic promoters |
+ | * make thoughts about the whole storyboard of our presentation at the jamboree | ||
- | == 8 | + | === 10-8-2009 === |
+ | * Short Meeting with Roland | ||
+ | * image processing work for wiki | ||
- | + | === 10-9-2009 === | |
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
- | + | === 10-12-2009 === | |
- | + | === 10-13-2009 === | |
+ | * Measurement discussion with Lars: REU/RMPU, defining equations for mammalian systems | ||
+ | * literature work on PoPS paper (Kelly JR et al.) and apply their equations | ||
+ | * Marti Modeling Meeting (Anna-Lena, Tim, Nao) | ||
+ | ** Journal Club (Tim, Nao) | ||
+ | ** summary of meeting from Team Meeting from last thursday | ||
- | * | + | * Marti: start modeling using MATLAB and Fuzzy Logic Toolbox (FLT), playing around with FLT and tutorial |
- | + | ||
- | == | + | === 10-14-2009 === |
- | + | Nao | |
+ | * develop first test fuzzy inference system (FIS) for testing | ||
+ | * Marti Modeling Meeting, specify model topology | ||
+ | * collect data: FACS (Cori), Microscopy (Hannah), Sequence & TECAN (Lars) | ||
+ | * start calculating position score using R | ||
+ | * translating project abstract | ||
- | * | + | === 10-15-2009 === |
- | + | Nao | |
+ | * calculate affinity score using TRAP (Anna-Lena) | ||
+ | * collect ideas for integrating TFwise scores in order to calculate final position/affinity score for one sequence: median, mean, maximum, weighted mean? | ||
+ | * all data analysis is stored in three sheets (SequenceAnalysis, ResultSummary and CalculateTRAP) | ||
+ | * from now on we concentrate on FACS measurements because they are the most reliable ones (TECAN used only for scanning) | ||
+ | * fill up TRAP data with missing transcription factors | ||
- | * | + | === 10-16-2009 === |
- | * | + | Nao |
- | * | + | * Anna-Lena Meeting: discuss how to integrate sequence scores |
- | * | + | * get & check p53, pPARg and random SREBP sequences |
+ | * go through FACS results | ||
+ | * add HEARTBEAT sequences for data analysis | ||
+ | * modeling documentation | ||
+ | * parsing experimental setups for modeling use | ||
+ | * Chenchen qRT-PCR results | ||
- | + | * define possible modeling layers | |
+ | ** first layer: input | ||
+ | *** drug type, pathway, drug mode of action, drug concentration, targeted cells, incubation time | ||
+ | *** sequence type, position score, affinity score | ||
+ | *** we choose position & affinity score, sequence type and the presence of stimulation. Time as well as different concentration (unfortunately no data available) can be added in future | ||
+ | ** second layer: promoters | ||
+ | *** 6 constitutives, 3 standards, 6 inducible available | ||
+ | *** data analysis narrows this to 5 constitutives, 3 standards and 4 inducible | ||
+ | *** HEARTBEAT sequences have to be measured a.s.a.p. | ||
- | * | + | * Marti Modeling Meeting |
- | * | + | ** try to define some fuzzy rules |
- | + | ** we assume better binding -> better expression | |
+ | ** define membership functions | ||
+ | ** start modeling with NFkB results | ||
- | * | + | All |
+ | * Internal Team Meeting | ||
+ | ** reminder: wiki task, wiki to do | ||
+ | * Official Team Meeting | ||
- | == | + | === 10-17-2009 === |
- | + | * final decision: we go for maximum of position and affinity score | |
+ | * added HB sequences for data analysis table; as soon as results are there we can model designed synthetic promoters | ||
+ | * define shape of membership functions | ||
+ | * literature search for missing activity values? | ||
+ | * still TODO: check out p53 results since the p53-NFkB crosstalk is really interesting! | ||
- | * | + | === 10-18-2009 === |
- | * | + | Nao |
- | * | + | * SREBP/VDR paper arrived |
+ | * finish data analysis | ||
+ | * study & playing around with MATLAB FLT, programming from both FLT GUI and MATLAB command line | ||
+ | * define our work to be (i) error checking and (ii) exclusive pathway modeling | ||
+ | * high potential of this model lies in its plug'n'play structrue, with a high capacity of integrating more inputs, outputs and also the middle layer (promoter diversity) | ||
+ | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | ||
- | == | + | === 10-19-2009 === |
+ | Nao | ||
+ | * define final network structure | ||
+ | * wiki work | ||
+ | * reading RFC documentation and correction | ||
+ | * we call this project HEARTBEAT fuzzy network (FN) | ||
+ | * HB FN documentation and first results! | ||
+ | ** creating two fuzzy controllers: inducible NFkB and constitutive | ||
+ | * how do we integrate the data? combine via Simulink! | ||
- | + | === 10-20-2009 === | |
+ | * Creating, developing, integrating and combining fuzzy network modeling (MATLAB, Simulink) | ||
+ | * first analysis of HB sequences | ||
+ | * HEARTBEAT FN documentation | ||
- | + | === 10-21-2009 === | |
- | + | ||
- | == | + | === 10-22-2009 === |
- | + | * FROZEN WIKI!!!! | |
- | + | [[https://2009.igem.org/Team:Heidelberg/Notebook_modeling TOP]] | |
- | + | ||
- | + | ||
- | |width="250px" style="background-color:#d8d5d0"| | + | |width="250px" style="padding: 0 20px 15px 15px; background-color:#d8d5d0"| |
|} | |} |
Latest revision as of 01:43, 22 October 2009
Notebook HEARTBEATWelcome to the notebook of the HEARTBEAT (Heidelberg Artificial Transcription Factor Binding Sites Assembly and Engineering Tool) project. This notebook comprises the work on three sublanes: HEARTBEAT database (DB), HEARTBEAT graphical user interface (GUI) and HEARTBEAT fuzzy modeling (FN) as well as some additional work on logo as well as wiki design. Have fun! ContentsJuly7-27-2009
[TOP] August
[TOP] 8-3-2009
8-4-2009
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8-7-2009
[TOP] 8-10-2009
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8-14-2009
[TOP] 8-18-2009Tim, Stephen, ab hier müsst ihr eure Sachen selber eintragen!
8-19-2009
8-20-2009
8-21-2009
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8-25-2009
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[TOP] 8-31-2009[TOP] September
[TOP] 9-1-2009
9-2-2009
9-3-2009
9-4-2009
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9-6-2009
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9-8-2009
9-9-2009
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9-11-2009
[TOP] 9-14-2009
9-15-2009
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9-18-2009[TOP] 9-20-2009
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[TOP] October
10-1-2009
10-2-2009
[TOP] 10-5-200910-6-2009
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10-9-2009[TOP] 10-12-200910-13-2009
10-14-2009Nao
10-15-2009Nao
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All
10-17-2009
10-18-2009Nao
[TOP] 10-19-2009Nao
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10-21-200910-22-2009
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