TY - JOUR
T1 - ALAN is a computational approach that interprets genomic findings in the context of tumor ecosystems
AU - Bergom, Hannah E.
AU - Shabaneh, Ashraf
AU - Day, Abderrahman
AU - Ali, Atef
AU - Boytim, Ella
AU - Tape, Sydney
AU - Lozada, John R.
AU - Shi, Xiaolei
AU - Kerkvliet, Carlos Perez
AU - McSweeney, Sean
AU - Pitzen, Samuel P.
AU - Ludwig, Megan
AU - Antonarakis, Emmanuel S.
AU - Drake, Justin M.
AU - Dehm, Scott M.
AU - Ryan, Charles J.
AU - Wang, Jinhua
AU - Hwang, Justin
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Gene behavior is governed by activity of other genes in an ecosystem as well as context-specific cues including cell type, microenvironment, and prior exposure to therapy. Here, we developed the Algorithm for Linking Activity Networks (ALAN) to compare gene behavior purely based on patient -omic data. The types of gene behaviors identifiable by ALAN include co-regulators of a signaling pathway, protein-protein interactions, or any set of genes that function similarly. ALAN identified direct protein-protein interactions in prostate cancer (AR, HOXB13, and FOXA1). We found differential and complex ALAN networks associated with the proto-oncogene MYC as prostate tumors develop and become metastatic, between different cancer types, and within cancer subtypes. We discovered that resistant genes in prostate cancer shared an ALAN ecosystem and activated similar oncogenic signaling pathways. Altogether, ALAN represents an informatics approach for developing gene signatures, identifying gene targets, and interpreting mechanisms of progression or therapy resistance.
AB - Gene behavior is governed by activity of other genes in an ecosystem as well as context-specific cues including cell type, microenvironment, and prior exposure to therapy. Here, we developed the Algorithm for Linking Activity Networks (ALAN) to compare gene behavior purely based on patient -omic data. The types of gene behaviors identifiable by ALAN include co-regulators of a signaling pathway, protein-protein interactions, or any set of genes that function similarly. ALAN identified direct protein-protein interactions in prostate cancer (AR, HOXB13, and FOXA1). We found differential and complex ALAN networks associated with the proto-oncogene MYC as prostate tumors develop and become metastatic, between different cancer types, and within cancer subtypes. We discovered that resistant genes in prostate cancer shared an ALAN ecosystem and activated similar oncogenic signaling pathways. Altogether, ALAN represents an informatics approach for developing gene signatures, identifying gene targets, and interpreting mechanisms of progression or therapy resistance.
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U2 - 10.1038/s42003-023-04795-1
DO - 10.1038/s42003-023-04795-1
M3 - Article
C2 - 37059746
AN - SCOPUS:85152578084
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 417
ER -