This guide will take approximately 10 minutes to complete.
The Multi-hop module is a very powerful hypothesis generation tool. Using this module, you can explore how two concepts are indirectly associated. For example, which are the potential mediators between a gene and a disease, and investigate supporting evidence.
In this guide you will:
- Learn how to find the potential mediators between two concepts of interest
- Apply filters to refine your search
- Deep dive into the evidence and visualize the results
Step 0: Login
Refer to https://med.causaly.com
TIP! In case you forgot your password, you can recover it here.
Step 1: Open the Multi-hop Search Module
Hover over the “Search” tab in the Causaly home page to access the Multi-hop module (Figure 1).
Figure 1: Select ‘’Multi-hop’’ search from the Causaly homepage.
In the Multi-hop Module, you will see a layout with three concept boxes, as indicated in Figure 2.
Figure 2: The Multi-hop module layout.
Let’s see an example in practice: We will explore how the Tumor Necrosis Factor (TNF) human protein induces Multiple Sclerosis (MS), and look for the potential implicated mechanisms.
TIP! To identify the potential mediators, we will use the direction A → B → C. Depending on your query, you can use other directionalities, such as in the following cases:
- A ← B → C: Mediators implicated in the pathogenesis of two diseases (e.g. Hormones (B) affecting MS (A) and Amyotrophic Lateral Sclerosis (C))
- A → B ← C: Common effects of two pharmacological substances (e.g. Side effects (B) caused by both sorafenib (A) and lenvatinib (C))
- A ← B ← C: Potential mechanisms by which a disease can be treated by a pharmacological substance (e.g. Proteins (B) that are affected by natalizumab (C) and affect the treatment of MS (A)
Step 2: Fill in boxes A and C with specific Concepts
Since we are interested in identifying mediators between TNF and MS, we will fill in boxes A and C.
Concept Box A
Begin your search by typing ‘’TNF’' in Box A and hit "Search" on the right.
TIP! When typing a term of interest, in this case TNF, and hit search, the system will suggest relevant concepts, as illustrated in Figure 3. Select one or more according to your research question. To find out more about searching effectively on Causaly, click here.
For this example, we will select only the first, “tnf, protein human”, since we are interested in the TNF protein family.
Figure 3: The relevant concepts when searching for ‘’TNF’’ in Box A. The ‘’COUNT(SUM)’’ column indicates the number of outgoing relationships, based on the outgoing relationship direction (A → B → C) for Box A.
Concept Box C
Fill in Box C with “Multiple Sclerosis” and hit "Search" on the right.
Likewise, when you type ‘’Multiple Sclerosis’’, the system suggests several relevant concepts and you can select the most appropriate one(s) for your query. In this example, we will select the broader Concept of Multiple Sclerosis and not focus on specific subtypes (Figure 4).
Click APPLY.
Figure 4: The relevant concepts that the system suggests when searching for ‘’Multiple Sclerosis’’ in Box C.
Step 3: Select the relevant Categories in Box B
In the Multi-hop module, apart from typing a concept, there is the option to choose specific categories relevant to your question, under the ‘’Category’’ tab.
Click on Box B and select the ‘’Category’’ tab.
To investigate the interfering mediators and pathways that relate TNF and MS, select the following categories: “Gene or Genome” found under “genes and molecular sequences”, as well as “cell function” and “molecular function” under “Physiology”(Figure 5) and click "Apply" at the bottom of your screen.
Figure 5: Refining the search by selecting specific UMLS filters under the ‘’Category’’ tab.
TIP! Depending on what you are looking for, or what type of mediators are of interest to you, you can select other categories such as ‘’cells’’ and ‘’tissues’’ below the ‘’Anatomy’’ category, ‘’Amino Acids, peptides or proteins’’ below ‘’Chemicals and Drugs’’ and/or ‘’Biologic function’’ below ‘’Phenomena’’ category.
Step 4: Click "SEARCH"
Results are presented in a grid view and sorted by descending Evidence Count. At the top, you can see the relationships with the most evidence (link).
TIP! You can also order your results by ascending Evidence Count or the Evidence Score or visualize your results by selecting the NETWORK view (Figure 6).
Figure 6: The network view between TNF human protein and multiple sclerosis
If you find something that may be of interest to you, you can either click on the arrow between the two concepts in the grid view or click on the line connecting the two branches of the network to explore the supporting evidence.
Step 5: Explore a Relationship of interest
Explore the results and identify potential mediators between TNF and MS in the “Concept B”(middle) column.
For a mediator of interest, such as “positive regulation of NF-kappa B transcription factor activity”, click on the left upregulate arrow to see how TNF affects NF-kappa B or the right upregulate arrow, next to ‘’Multiple Sclerosis’’ to explore how it affects the disorder (Figure 7).
Above each arrow you can find the amount of evidence existing between two concepts. In this example, you can see that there is a lot more evidence between TNF and NF-kappa B activity (298 evidence points) than NF-kappa B activity and MS (19 evidence points).
Figure 7: Selecting the relationship between NF-kappa B activity and TNF/MS to explore
By clicking the relevant arrows, you will find the supporting evidence points related to the implication of an increased NF-kappa B activity to TNF/Multiple Sclerosis (Figure 8).
Figure 8: Evidence points presented in the sidebar
Want to learn more about how to find evidence in Causaly?
Find more information and examples on step-by-step guides by clicking here.