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Inference of mutational signature activity in individual tumors

DL David Liu
PA Philip Abbosh
DK Daniel Keliher
BR Brendan Reardon
DM Diana Miao
KM Kent Mouw
AW Amaro Weiner-Taylor
SW Stephanie Wankowicz
GH Garam Han
MT Min Yuen Teo
CC Catharine Cipolla
JK Jaegil Kim
GI Gopa Iyer
HA Hikmat Al-Ahmadie
ED Essel Dulaimi
DC David Y. T. Chen
RA R. Katherine Alpaugh
JH Jean Hoffman-Censits
LG Levi A. Garraway
GG Gad Getz
SC Scott L. Carter
JB Joaquim Bellmunt
EP Elizabeth R. Plimack
JR Jonathan E. Rosenberg
EA Eliezer M. Van Allen
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Given a set of mutational signatures, inferring the activity of each mutational signature within individual tumors was performed by modifying the NMF multiplicative update process15,58. We randomly initialize a starting activity matrix H0 and update Hi to Hi+1 via the multiplicative update rule given for H15. W remains fixed and so is not updated. We keep track of the Frobenius norm of the error given by V-WHi at each iteration. We terminated the update process when error vs. iterations demonstrated horizontal asymptomatic behavior, which we defined as when 1/20 of the difference of the error between V-WHi-20 and V-WHi is below a given threshold (0.0001). The resulting matrix Hi is a good representation of the activity of the signatures in W.

Copyright and License information: The Author(s) ©2017
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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