What do senders, receivers, mediators and influencers mean?

[newcounts]

Hi，
The output graph of function netVisual_signalingRole has senders, receivers, mediators and influencers. But I don’t understand the exact meaning of mediators and influencers. How those cell acts as a(n) mediator and/or influencer.

thanks.
best wish

[sqjin]

@newcounts Hello, the mediator score is quantified by flow betweenness metric from graph theory. Intuitively, it measures a group of cells’ capability as gatekeeper to control communication flow between any two cell groups. The influencer is quantified by a hybrid measure called information centrality. Basically, for information flow within a signaling network, a higher value indicates greater influence on the information flow. The diagram in Figure 1e is helpful for understanding such measures. We also described these measures in the Method section.

[MMriran]

Hi，I had noticed that in your paper you methioned that “the majority of TGFβ interactions among wound cells are paracrine, with only one fibroblast and one myeloid population demonstrating significant autocrine signaling”,how can I get such information from the heatmap (fig2b in your paper)?

[sqjin]

Hi @MMriran, in fig2b, slightly higher scores of both Sender and Receiver for FIB-D suggest that FIB-D is the autocrine signaling. The same case is for MYL-A population.

[gynecoloji]

@sqjin
Hi Dr. sqjin,

Thanks for your clarification for differences between mediators and influencers. But I still do not understand the real difference between them even if you tell me how you calculate it. Because I am not a mathematician and do not fully understand the metrics used in your calculation. I am sorry about it.
So Could you please clarify them with more obvious words?

Sincerely,

Ji

[sqjin]

Hi @gynecoloji , these measures are indeed similar, and both of them can represent the importance of cell groups in controlling the communication flow. But I think they emphasis on different aspects. In particularly, mediators is quantified by 'betweeness', which has been widely used to indicate the importance of nodes in the network. You might can simply google it and learn more about it (https://en.wikipedia.org/wiki/Betweenness_centrality). From our Figure 1e, you might can find some slightly differences between mediators and influencers. You can also learn about from the references in our paper.

[jv-20]

Hi @sqjin, a quick question in relation to accessing results mediator & influencer scores.

For example, when I do cellchat.obj@netP$centr$ I can access the centrality measures such as outdegree, indegree, hub, authority, eigen, page_rank ,betweeness, flow_between and info.

I am trying to extract the scores for mediators and influencers. In the paper you mentioned flow betweeness is used for identifying mediators. May I ask what is the other score called "betweeness" used for?

Is the value for influencers stored in the cellchat results? In the paper you mentioned "Information centrality score provides a hybrid measure, for example by combining closeness and eigenvector". I see object stored named eigen but not closeness. Could you please advice how to access the value for closeness?

Thank you, apologies if I am asking the obvious. Would appreciate your thoughts.

[sqjin]

Hi @jv-20 , the other score "betweenness" is a classic concept/measure in the graph theory. You can simply search it online.

The influencers can be accessed via centr$info. You can check the documentation of netVisual_signalingRole to see the measures and the corresponding new names. CellChat does not compute the closeness metric.

[jv-20]

Many thanks @sqjin. The documentation is helpful, thank you

[sunny-yangyang]

Thanks for creating this excellent tool and giving us such detailed explanation. But I'm still confused about the biological roles of Mediator and Influencer. If Sender can be seen as the Ligand, Receiver can be seen as the Receptor, How about the role and function of Mediator and Influencer in cell-cell communication? Does Mediator can be seen as the Cofactor or anything else? Could you please provide an example of the Mediator and Influencer in a specific pathway? Thank you soooo much!

[sunny-yangyang]

Thanks for creating this excellent tool and giving us such detailed explanation. But I'm still confused about the biological roles of Mediator and Influencer. If Sender can be seen as the Ligand, Receiver can be seen as the Receptor, How about the role and function of Mediator and Influencer in cell-cell communication? Does Mediator can be seen as the Cofactor or anything else? Could you please provide an example of the Mediator and Influencer in a specific pathway? Thank you soooo much!

Sorry to correct my question, If Sender could express Ligand, Receiver could express Receptor, Does Mediator or Influencer express different moleculars such as Agonist/Antagonist OR Agonist/Antagonist Receptor? I just wonder the difference roles between Mediator and Influencer in cell-cell communication pathway. Sorry to interupt you if my questions are silly and still looking forward your reply, Thank you so much~

[sqjin]

Thanks for creating this excellent tool and giving us such detailed explanation. But I'm still confused about the biological roles of Mediator and Influencer. If Sender can be seen as the Ligand, Receiver can be seen as the Receptor, How about the role and function of Mediator and Influencer in cell-cell communication? Does Mediator can be seen as the Cofactor or anything else? Could you please provide an example of the Mediator and Influencer in a specific pathway? Thank you soooo much!

Sorry to correct my question, If Sender could express Ligand, Receiver could express Receptor, Does Mediator or Influencer express different moleculars such as Agonist/Antagonist OR Agonist/Antagonist Receptor? I just wonder the difference roles between Mediator and Influencer in cell-cell communication pathway. Sorry to interupt you if my questions are silly and still looking forward your reply, Thank you so much~

These measures are used to quantify the importance of cell types in certain effect and they do not represent any molecules. Cell types with high sender scores suggests they are the major signaling sources.

[sunny-yangyang]

Thank you very much for answering my questions! So the Sender could express signal molecule not only Ligand but also co-factors like Agonist/Antagonist, which means the Signal Source? Besides, Receiver could express not only Receptor but also Agonist/Antagonist Receptor? Could you please tell me if I understand the situation correctly?

…

------------------&nbsp;原始邮件&nbsp;------------------ 发件人: "sqjin/CellChat" <[email protected]&gt;; 发送时间:&nbsp;2020年12月12日(星期六) 下午3:57 收件人:&nbsp;"sqjin/CellChat"<[email protected]&gt;; 抄送:&nbsp;"846720602"<[email protected]&gt;;"Comment"<[email protected]&gt;; 主题:&nbsp;Re: [sqjin/CellChat] What do senders, receivers, mediators and influencers mean? (#7) Thanks for creating this excellent tool and giving us such detailed explanation. But I'm still confused about the biological roles of Mediator and Influencer. If Sender can be seen as the Ligand, Receiver can be seen as the Receptor, How about the role and function of Mediator and Influencer in cell-cell communication? Does Mediator can be seen as the Cofactor or anything else? Could you please provide an example of the Mediator and Influencer in a specific pathway? Thank you soooo much! Sorry to correct my question, If Sender could express Ligand, Receiver could express Receptor, Does Mediator or Influencer express different moleculars such as Agonist/Antagonist OR Agonist/Antagonist Receptor? I just wonder the difference roles between Mediator and Influencer in cell-cell communication pathway. Sorry to interupt you if my questions are silly and still looking forward your reply, Thank you so much~ These measures are used to quantify the importance of cell types in certain effect and they do not represent any molecules. Cell types with high sender scores suggests they are the major signaling sources. — You are receiving this because you commented. Reply to this email directly, view it on GitHub, or unsubscribe.

[sunny-yangyang]

In addtion, I just wondering if the "contribution of each L-R ligand "(Fig 2c,2e in your bioRxiv preprint 10.1101/2020.07.21.214386) includs all the factors such as Ligand/Receptor and co-factors like Agonist/Antagonist, co-stimulatory/co-inhibitory Receptor?

…

------------------&nbsp;原始邮件&nbsp;------------------ 发件人: "sqjin/CellChat" <[email protected]&gt;; 发送时间:&nbsp;2020年12月12日(星期六) 下午3:57 收件人:&nbsp;"sqjin/CellChat"<[email protected]&gt;; 抄送:&nbsp;"846720602"<[email protected]&gt;;"Comment"<[email protected]&gt;; 主题:&nbsp;Re: [sqjin/CellChat] What do senders, receivers, mediators and influencers mean? (#7) Thanks for creating this excellent tool and giving us such detailed explanation. But I'm still confused about the biological roles of Mediator and Influencer. If Sender can be seen as the Ligand, Receiver can be seen as the Receptor, How about the role and function of Mediator and Influencer in cell-cell communication? Does Mediator can be seen as the Cofactor or anything else? Could you please provide an example of the Mediator and Influencer in a specific pathway? Thank you soooo much! Sorry to correct my question, If Sender could express Ligand, Receiver could express Receptor, Does Mediator or Influencer express different moleculars such as Agonist/Antagonist OR Agonist/Antagonist Receptor? I just wonder the difference roles between Mediator and Influencer in cell-cell communication pathway. Sorry to interupt you if my questions are silly and still looking forward your reply, Thank you so much~ These measures are used to quantify the importance of cell types in certain effect and they do not represent any molecules. Cell types with high sender scores suggests they are the major signaling sources. — You are receiving this because you commented. Reply to this email directly, view it on GitHub, or unsubscribe.

[sqjin]

In addtion, I just wondering if the "contribution of each L-R ligand "(Fig 2c,2e in your bioRxiv preprint 10.1101/2020.07.21.214386) includs all the factors such as Ligand/Receptor and co-factors like Agonist/Antagonist, co-stimulatory/co-inhibitory Receptor?
…
------------------ 原始邮件 ------------------ 发件人: "sqjin/CellChat" <[email protected]>; 发送时间: 2020年12月12日(星期六) 下午3:57 收件人: "sqjin/CellChat"<[email protected]>; 抄送: "846720602"<[email protected]>;"Comment"<[email protected]>; 主题: Re: [sqjin/CellChat] What do senders, receivers, mediators and influencers mean? (#7) Thanks for creating this excellent tool and giving us such detailed explanation. But I'm still confused about the biological roles of Mediator and Influencer. If Sender can be seen as the Ligand, Receiver can be seen as the Receptor, How about the role and function of Mediator and Influencer in cell-cell communication? Does Mediator can be seen as the Cofactor or anything else? Could you please provide an example of the Mediator and Influencer in a specific pathway? Thank you soooo much! Sorry to correct my question, If Sender could express Ligand, Receiver could express Receptor, Does Mediator or Influencer express different moleculars such as Agonist/Antagonist OR Agonist/Antagonist Receptor? I just wonder the difference roles between Mediator and Influencer in cell-cell communication pathway. Sorry to interupt you if my questions are silly and still looking forward your reply, Thank you so much~ These measures are used to quantify the importance of cell types in certain effect and they do not represent any molecules. Cell types with high sender scores suggests they are the major signaling sources. — You are receiving this because you commented. Reply to this email directly, view it on GitHub, or unsubscribe.

The contribution of each L-R ligand is calculated based on the overall communication probability (i.e., sum of all the weights) of the inferred network. It is NOT related with any signaling molecule!

[gAleryani]

Hi @sqjin ,
Great tool! And the manual / vignette is very comprehensive, great to look at for the analysis of all kinds of research scenarios. :)

I do think though that some more explanation for how to interpret the data is required, one that is within the context of cellular biology, after all, the tool is called "CellChat". Even after reading this board I still do not fully comprehend what the difference between "mediator" and "influencer" is, this within the practical context of cell-cell interaction of any system like let's say the tumour microenvironment or organ development.

I would really appreciate an explanation! Thanks in advance for your time :)

[sunny-yangyang]

您好，您的邮件我已经收到，非常感谢！很抱歉现在不能立即回复您，我会尽快阅读和处理此邮件并与您联系。Dear sender,Thank you for your email.I will reply you as soon as I've handled it.

[Lucky-Yangyang]

Hi@MMriran，in fig2b, slightly higher scores of both Sender and Receiver for FIB-D suggest that FIB-D is the autocrine signaling. The same case is for MYL-A population.
Hi @sqjin ,
In fig2b, the scores of FIB-D in Mediator and Influencer are significantly higher than those in Sender and Receiver, why suggest that FIB-D is the autocrine signaling? Could I comprehend if a cell type have both Sender and Receiver score, even though that is not so high, which is a autocrine signaling? And if a cell type have Sender or Receiver or none of them , even though the score of Sender or Receiver is so high, which still mean that is a paracrine signaling?

[sunny-yangyang]

您好，您的邮件我已经收到，非常感谢！很抱歉现在不能立即回复您，我会尽快阅读和处理此邮件并与您联系。Dear sender,Thank you for your email.I will reply you as soon as I've handled it.

[sqjin]

Hi@MMriran，in fig2b, slightly higher scores of both Sender and Receiver for FIB-D suggest that FIB-D is the autocrine signaling. The same case is for MYL-A population.
Hi @sqjin ,
In fig2b, the scores of FIB-D in Mediator and Influencer are significantly higher than those in Sender and Receiver, why suggest that FIB-D is the autocrine signaling? Could I comprehend if a cell type have both Sender and Receiver score, even though that is not so high, which is a autocrine signaling? And if a cell type have Sender or Receiver or none of them , even though the score of Sender or Receiver is so high, which still mean that is a paracrine signaling?

autocrine signaling means the signaling among Fibroblasts and this is not related with Mediator/Influencer.