Documentation
Ageing clusters consist of different pages that you can access using the tabs in the horizontal menu bar. The following sections describe the individual pages in more detail.
Genes
The genes page lists the different gene sets that are used in our resource. For the sake of brevity, we use the term gene to refer to a gene and all its gene products. All the data we incorporate into Ageing clusters are unifying based on Entrez Gene IDs. As a result of one-to-many mappings (e.g. between genes and protein isoforms, but also between gene identifiers and human gene symbols), there can be ambiguities, e.g., resulting in multiple network nodes with the same gene symbols or network nodes with multiple gene symbols.
The core of Ageing clusters are the 35 datasets that report different types of ageing associations, we refer to those as Panels. Highlight datasets may provide additional gene annotations, e.g., data about drug targets.
All tables can be sorted by clicking on a particular respective column header. Certain columns are linked to external databases, such as Entrez, UniProt, or PubMed, via their respective identifiers. All the interaction networks involving a certain gene can be requested by clicking on the Search at the beginning of a table row table row.
You can download the complete datasets for detailed analyses via the link provided on the genes page. The files in this archive may contain more associations than those listed on the website, as genes in highlight dataset are only listed on the webiste if they are present in any of the networks. Panel gene sets are shown without any filtering, thus there is no difference between the website version and the file available for download.
Networks
The networks page links the genes from the different gene sets in various molecular interaction networks. The page is roughly divided into three areas:
- a network selection area on the top,
- the network visualization in the center,
- and the network annotation tabs at the bottom.
Network types & network selection
Ageing clusters uses different underlying networks and the meaning of edges will differ depending on the particular network. In bioplex an edge indicates part of a protein complex, in mentha it represents a binary protein interaction or a protein complex, in STRING (string_0.9) it can be a protein interaction or a functional association, in funsimbp it represents a high functional similarity between two gene products. In addition to the individual networks, we also use a combined network of bioplex, mentha, and string_0.9. Please have a look at the versions section below for more details on all interaction datasets.
The network selection area is composed of different categories that can be opened and closed by clicking on them. For each of the networks we provide a brief summary, e.g. listing how many nodes and edges it contains and how man genes are annotated to different datasets. The network category Clusters in full networks lists all relevant clusters in the underlying networks. Network clusters are parts of the network that are more densely connected than the surrounding areas. We use the software ClusterONE to detect network clusters, relevant network clusters are those that contains at least one panel gene.
Network visualization
The network browser is based on the Cytoscape.js library. By default the network browser is empty and a network has to be selected by the user. Once a network has been selected, the visualization rules are:
- Fill color: By default nodes are filled with grey color. ARD genes are filled with a gold background.
- Border color: By default nodes have no border. Genes in an AGE set have a solid red border, genes in a ME set a dotted violet border, and genes that are in both AGE and ME have a red dotted border.
- Text color: By default nodes have a black label showing the HGNC gene symbols associated with the respective node. Genes that are reported in an EX set have a blue label text.
- Node shape: By default nodes are drawn as rectangles. Drug targets are drawn as octagons.
- Selection: When nodes or edges are selected (e.g. either by clicking on them, using the search box or by selecting entries from a table), all unselected elements become half-transparent.
- AGE = red solid border
- ARD = golden fill.
- EX = blue text color.
- ME = violet dotted border, red dotted border in combination with AGE.
- Drug targets: octagonal shapes
Network navigation
For navigating the network you can use your mouse (zooming, panning, selecting) or the bar on the left (zooming, panning). To request additional information in a particular node or edge, click on the respective item to retrieve a popup window. Node popups will contain identifiers, gene sets, functional information from the Gene Ontology, and an option to select neighboring nodes. Edge popups will list the interaction source, the PubMed identifier of the literature reference (if available), a confidence score (if available), and the option to select the two nodes that are connected by the edge. You can close a popup either with the top-right X or by clicking anywhere on the white network background, which will also remove the selection. You can select multiple nodes by holding the shift button before clicking on the node. Node selections in the network visualization are connected to the annotation tabs below, selected nodes are marked in a bold orange text. Vice versa, you can use the select buttons in the annotation table to select network nodes in the visualization. Node selections will also be encoded in the URL that is shown in your browser. As a result, you can save the current URL, e.g., to share a network and its selections with a colleague.
Network annotations
Below the network visualization you will find a number of annotation tabs providing further information for currently visualized network.
- Selected genes will provide the gene-based information for all the genes currently selected in the network. If more than one gene is selected, you will need to open/close the respective entries by clicking on them. The information listed here is the same that you would get in the network popups, only in an expanded form.
- Network info, which is open by default, shows some basic network information such as number of nodes or edges. It will also show all the different gene sets and list the nodes from the respective sets that are present in the network, with the option to select all the nodes in the network.
- The next three tabs (Biological processes, Cellular components, Molecular functions) list all the GO annotations of all the genes in the network. As for all other tables, you can sort them by a column if you click on the respective header. The List of genes column can be expanded/collapsed by clicking on the header, individual table cells will be expanded when you hover the mouse over an element that ends with '...'. The button in the last column will select all the nodes that are annotated with a certain term in the network. As mentioned before, the visualization and the table are linked, if you select a gene in the network the gene name will also be colored differently in the table below.
- BP Enrichment lists all GO BP annotations that are significantly enriched in the current network, when comparing to the annotations of the whole underlying background with a false discovery rate adjusted p-value < 0.05. For some networks this information might not be available.
Search
The search tab allows you to search across the whole Ageing clusters website. At the moment this search is gene-centered, i.e., will only find gene-related information such as parts of gene names or synonyms, database identifiers (Entrez, UniProt), or names of gene sets (e.g. Input). Search results will include any references to matching entries in the genes and networks tabs, that is, when you click on one of the network links, you will be directed to the respective network with the query gene already selected.
Data sources, tools, and versions Below we list all the data sources and software tools that we used to build Ageing clusters. For the sake of reproducibility, we also list the particular versions where available.
| Name & Link | Description | Version | Reference |
|---|---|---|---|
| BioPlex | Protein interactions (co-complex associations from large-scale experiment) | v4 | Huttlin et al., 2015 |
| mentha | Protein interactions (binary interaction & co-complex associations, curated from the literature & experiments) | Human (9606) release 20151127 | Calderone et al., 2013 |
| STRING | Protein interactions and functional relations (binary interaction & co-complex associations, curated from the literature & experiments & computationally predicted) | v10, requiring confidence score >= 900 (string_0.9) | Szklarczyk et al., 2014 |
| DrugBank | Drug targets | 5.0.3 | Wishart et al., 2006 |
| Gene Ontology | Gene annotations | 2015.09 | Ashburner et al., 2000 |
| ClusterONE | Tool for network cluster detection | Java version 1.0 | Nepusz et al., 2012 |
| Cytoscape.js | Tool for network visualization | 2.6.7 | Franz et al., 2016 |
| igraph | Tool for network analysis and extraction | python-igraph 0.7.0 | Csardi and Nepusz, 2006 |
| Dintor | Tool for various computations, e.g., identifier conversion | Weichenberger et al., 2015 |