TiCoNE

Time Course Network Enricher is an interactive clustering method for time-series data
Categories: clustering, data visualization, enrichment analysis, systems biology
TiCoNE is a tool for the combined analysis of time series expression data together with biological networks. Check out the web site ([https://ticone.compbio.sdu.dk]) for a screen cast and step-by-step tutorials. TiCoNE accepts time resolution expression data tables (for one or more replicates, patients, or samples) and maps the time courses onto the genes/proteins in a selected Cytoscape network. Afterwards, one may use TiCoNE to cluster the time series sets (i.e. sets of time courses for each gene) iteratively. It provides functionality to interfere with the clustering iterations in an expert-supervised manner (see tutorial). TiCoNE computes error rates, p-values, permutations, etc. on the fly and allows the time course data sets to be sorted and investigated (merging, splitting, noise reduction). Finally, one may enrich the data sets by selecting gene clusters with similar time course behavior, which will be mapped onto the loaded network in order to find sub-networks enriched with genes that have related expression patterns over time. *Bugs or feature requests* can be posted in our tracker: https://gitlab.com/ticone/ticone-cy/issues ***Citation:*** Wiwie C, Kuznetsova I, Mostafa A, Rauch A, Haakonsson A, Barrio-Hernandez I, Blagoev B, Mandrup S, Schmidt HHHW, Pleschka S, Röttger R, Baumbach J (2019) Time-resolved systems medicine reveals viral infection-modulating host targets, Systems Medicine 2:1, 1–9, DOI: 10.1089/sysm.2018.0013.
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2.0.0

Works with Cytoscape 3.7

Release Notes

- New feature: Added composite similarity functions and composite prototypes - More infos here: https://arxiv.org/abs/1904.12353 - New feature: Added cluster similarity network - New feature: Seed value for clustering can be set to ensure completely reproducible results, including p-values - New feature: When calculating cluster p-values, feature value distributions can be stored and visually inspected - Improvement: Batch network enrichments now store multiple networks in a collection - Bugfix: Improved threadsafeness of many operations - Many major and minor improvements and bugfixes

1.3.79

Works with Cytoscape 3.2

Release Notes

- When calculating cluster p-values, the features for the cluster fitness score can now be manually specified - Bugfix: Fixed a problem with coloring of clusters in the zoom window and the network view - Bugfix: Fixed cluster IDs when reloading an existing session

1.3.77

Works with Cytoscape 3.2

Release Notes

- Added multiple ways to calculate background distributions for p-value calculations - Added function to delete old clustering iterations (reduce memory use) - Added filter functionality for clusters - Cluster p-values are no longer calculated for every clustering automatically; They can be calculated using the cluster p-value form on the Cluster Operations tab; - Merged three checkboxes for each cluster into one checkbox - Added new sorting attributes for clusters (e.g. prototype variance) - Many performance improvements "under the hood" - Note: This release has breaking changes due to many internal refactorings and improvements. Thus, cytoscape sessions created with older versions of TiCoNE are not supported

1.2.74

Works with Cytoscape 3.2

Release Notes

- Bugfix: In case of very large networks, permutations for p-value calculation of connectivity were silently failing, leading to incorrect and very small p-values;

1.2.73

Works with Cytoscape 3.2

Release Notes

- Bugfix: For certain inputs, the connectivity expected edges and p-values were not calculated correctly; - Bugfix: Formula for directed expected edges between clusters was incorrect; - GUI: The edge table of the cluster connectivity networks now contain the cluster names; - Improvement: Import initial clustering from table now keeps the cluster IDs specified in the table; - Improvement: Most results now take much less memory than before; this should lead to a better usability and reponsiveness of Cytoscape when using TiCoNE with a lot of results or big data sets;

1.2.72

Works with Cytoscape 3.2

Release Notes

- Bugfix: PDF summary of all iterations was written to wrong path;

1.2.71

Works with Cytoscape 3.2

Release Notes

- Bugfix: Connectivity results were constantly overestimating the expected number of edges due to the usage of a knn-imputation of missing joined node degrees - removed the imputation for now; - GUI: Changed the layout of connectivity networks a bit, i.e. added more infos to the edges such as p-values or expected edges; - GUI: The network node coloring of clusters now creates a visual style, such that it is not lost every time the style of the network is manually changed;

1.2.70

Works with Cytoscape 3.2

Release Notes

- Adapted cluster connectivity p-value calculation: P-values are now with respect to observing an as extreme log-odds ratio, instead of the absolute number of edges between a pair of clusters; - Added export function for clusters of all iterations to the cluster summary panel; - Results (clusterings, comparisons, connectivities) can now be renamed by right-clicking on the tab; - GUI: Coloring of clusters changed: Clusters are now not collored according to their number in their clustering, but according to order of creation across all clusterings; this leads to more different colors being used in several clusterings; - GUI: Using collapsible panels to hide and group options and information;

1.2.69

Works with Cytoscape 3.2

Release Notes

- New: The aggregation function for cluster prototypes can be chosen when starting a new clustering. Available at the moment: Mean (default so far), median, most central object; - GUI: Cleaned up the "New Clustering" panel;

1.2.68

Works with Cytoscape 3.2

Release Notes

- New: Added two-sided permutation test for connectivity, now also cluster pairs with very low number of edges are considered significant; - New: The permutation function (object-wise / globally) can be chosen for clustering comparisons; - New: The edge swap factor influencing how many edge swaps are performed for each permuted network can be set by the user; - New: Initial clustering can now be imported from a table: One column containing the object id, a second column the cluster id; - Bugfix Edge crossover: We did not add a random edge from S to T, if it was already present in the original network; this lead to biased p-values; - Bugfix Edge crossover: We always kept source and target of the two randomly picked edges as we got them from Cytoscape; this could lead to biases if edges between pairs of clusters were stored preferrably in one direction in the table than the other; - Bugfix: Fixed variance filter; - Bugfix: Hiding and showing TiCoNE tabs on the control panel did not work properly when there were tabs in the result panel to the left of the TiCoNE tabs; - Bugfix: One empty, unused edge was added between each pair of clusters to undirected connectivity network; - Improved cluster p-values when using Euclidian distance; - GUI: Added better progress updates during "Iterations until convergence"; - GUI: Added button to cluster connectivity results panel to create connectivity networks; - GUI: Showing creation date for all clustering, comparison and connectivity results; - GUI: Showing number of permutations and edge swap factor on results panel for connectivity analysis if p-values were calculated; - GUI: Some cosmetical fixes and terminological changes;

1.2.67

Works with Cytoscape 3.2

Release Notes

- Bugfix: Corrected formula for expected number of edges for directed cluster connectivity; - Bugfix: Saving a session with a cluster connectivity result lead to an error and was empty when loaded again;

1.2.66

Works with Cytoscape 3.2

Release Notes

- Bugfix: An error occurred when a connectivity analysis was performed without permutation tests; - Improved cancellation of a cluster connectivity analysis: The process now stops faster; - GUI: Improved input handling when starting a cluster connectivity analysis: Only number of permutations > 0 are allowed;

1.2.65

Works with Cytoscape 3.2

Release Notes

- Bugfix: Cluster charts were not showing under Windows and Mac if not enough space was available; - Bugfix: Removing least fitting object sets dialog was not showing if initially 0 objects were selected for removal; - Bugfix: Loading clustering comparison network enrichments was not working properly;

1.2.64

Works with Cytoscape 3.2

Release Notes

- Nodes of node-induced networks have an attribute "inOriginalNetwork" indicating, whether they are contained in the original network ;

1.2.63

Works with Cytoscape 3.2

Release Notes

- Changed export format of clusters to a more readable format: each row consists of cluster id {tab} object id; - network enrichment result panel (KPM) shows for which clusters it has been performed (this is useful for batch network enrichments to better keep track which enrichments are for which clusters);

1.2.62

Works with Cytoscape 3.2

Release Notes

- Bugfix: Remove least varying objects with threshold did not work; - Showing total number of objects of clustering in the header of the clustering result table;

1.2.61

Works with Cytoscape 3.2

Release Notes

- Bugfix: Remove percentage of least varying objects was not working; - Preview chart of least varying objects / least conserved objects now shows all objects and not only 10;

1.2.60

Works with Cytoscape 3.2

Release Notes

- List to select time point columns can now be reordered using Drag & Drop to set the order of time point columns; - this order is used when performing new clusterings, clustering comparisons and cluster connectivity analyses; - previously, clustering comparisons could lead to wrong prototype similarities when the orderings of time point columns of two clusterings did not match;

1.2.59

Works with Cytoscape 3.2

Release Notes

- Improved error handling of invalid inputs; - Missing values (empty strings) not supported as of now; - Time point signals need to be numeric; - Object ids must not be empty; - Sample name must not be empty; - Each sample may only be present ones for each object; - Header line: Added option to parse first line of file as header when performing clustering "From File";

1.2.58

Works with Cytoscape 3.2

Release Notes

- Bugfix: Connectivity analysis and clustering comparisons may modify original clustering in certain cases (e.g. randomly ending up with empty clusters in new iterations);

1.2.57

Works with Cytoscape 3.2

Release Notes

- Bugfix: CLARA was not behaving deterministically; - Bugfix: Performing a clustering without a loaded network resulted in an error;

1.2.56

Works with Cytoscape 3.2

Release Notes

- Bugfix: Removing non-fitting objects lead to an error when clusters became empty; - Bugfix: When using CLARA or PAMK the numbering of clusters was messed up after calculating p-values;

1.2.55

Works with Cytoscape 3.2

Release Notes

- Bugfix: Falsely renamed "Clusters" in clustering result tab to "Cluster Operations";

1.2.54

Works with Cytoscape 3.2

Release Notes

- Bugfix: Filter objects dialogs did not show up; - Bugfix: Delete cluster objects dialogs did not show up; - Renamed Tabs in control panel to clarify their role;

1.2.53

Works with Cytoscape 3.2

Release Notes

- Clustering Comparison: Two clusterings can be compared by comparing pairs of clusters; for each cluster pair the actual number of common objects can be compared to the expected number of common objects; - Alternative IDs: A cytoscape table can be used to map alternative ids (e.g. gene names) to the clustered objects; - Column Mapping: When choosing the cytoscape table containing the time-series data, the columns for object ID, replicates and time points can now be configured; - GUI redesign: The graphical UI has been redesigned and made slimmer; TiCoNE now adds 3 separate result tabs to the Cytoscape result panel for clusterings, comparisons and connectivity analyses; - GUI: Cosmetic changes to cluster charts; - Breaking changes to saved sessions: Saved sessions of prior versions can not be loaded with this version.

1.1.44

Works with Cytoscape 3.2

Release Notes

- Several clusterings: Several clusterings can now be kept in different tabs. - Several network enrichments: Network enrichments are now stored for each clustering separately in a tabbed pane. Several network enrichments can be kept per clustering. - Batch Network Enrichment: It is now possible to perform Network Enrichment for each selected cluster independently and either automatically generate the union or core network of the resulting subnetworks. The Network Enrichment process uses the settings configured on the original KPM tab. - Cluster Connectivity: It is now possible to analyze the connectivity between the found clusters in the network. - It is now possible to manually specify which columns of the table / file contain object ids, replicates and time-points. - UI: Small graphs of clusters have smaller margins and thus more space for object time-series lines. - UI: Network Enrichment: Views are not automatically created any longer - UI: A click on the KPM, Merge or Visualize column header will select/deselect the whole column respectively. - Bugfix: Network lists was updated after destroying views and successive KPM execution failed. - Bugfix: Small graphs of clusters can now be correctly sorted by their prototype similarity.

1.1.42

Works with Cytoscape 3.2

CYTOSCAPE 3

Version 2.0.0

Released 1 May 2019

Works with Cytoscape 3.7

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