IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30449-7.html
   My bibliography  Save this article

An integral genomic signature approach for tailored cancer therapy using genome-wide sequencing data

Author

Listed:
  • Xiao-Song Wang

    (University of Pittsburgh
    University of Pittsburgh)

  • Sanghoon Lee

    (University of Pittsburgh
    University of Pittsburgh)

  • Han Zhang

    (University of Pittsburgh
    University of Pittsburgh)

  • Gong Tang

    (University of Pittsburgh)

  • Yue Wang

    (University of Pittsburgh
    University of Pittsburgh)

Abstract

Low-cost multi-omics sequencing is expected to become clinical routine and transform precision oncology. Viable computational methods that can facilitate tailored intervention while tolerating sequencing biases are in high demand. Here we propose a class of transparent and interpretable computational methods called integral genomic signature (iGenSig) analyses, that address the challenges of cross-dataset modeling through leveraging information redundancies within high-dimensional genomic features, averaging feature weights to prevent overweighing, and extracting unbiased genomic information from large tumor cohorts. Using genomic dataset of chemical perturbations, we develop a battery of iGenSig models for predicting cancer drug responses, and validate the models using independent cell-line and clinical datasets. The iGenSig models for five drugs demonstrate predictive values in six clinical studies, among which the Erlotinib and 5-FU models significantly predict therapeutic responses in three studies, offering clinically relevant insights into their inverse predictive signature pathways. Together, iGenSig provides a computational framework to facilitate tailored cancer therapy based on multi-omics data.

Suggested Citation

  • Xiao-Song Wang & Sanghoon Lee & Han Zhang & Gong Tang & Yue Wang, 2022. "An integral genomic signature approach for tailored cancer therapy using genome-wide sequencing data," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30449-7
    DOI: 10.1038/s41467-022-30449-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30449-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-30449-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J.Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Red, 2012. "Addendum: The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 492(7428), pages 290-290, December.
    2. Friedman, Jerome H. & Hastie, Trevor & Tibshirani, Rob, 2010. "Regularization Paths for Generalized Linear Models via Coordinate Descent," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 33(i01).
    3. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J. Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Re, 2012. "The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 483(7391), pages 603-607, March.
    4. Hothorn, Torsten & Lausen, Berthold, 2003. "On the exact distribution of maximally selected rank statistics," Computational Statistics & Data Analysis, Elsevier, vol. 43(2), pages 121-137, June.
    5. Benjamin Haibe-Kains & Nehme El-Hachem & Nicolai Juul Birkbak & Andrew C. Jin & Andrew H. Beck & Hugo J. W. L. Aerts & John Quackenbush, 2013. "Inconsistency in large pharmacogenomic studies," Nature, Nature, vol. 504(7480), pages 389-393, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Caitlin E. Mills & Kartik Subramanian & Marc Hafner & Mario Niepel & Luca Gerosa & Mirra Chung & Chiara Victor & Benjamin Gaudio & Clarence Yapp & Ajit J. Nirmal & Nicholas Clark & Peter K. Sorger, 2022. "Multiplexed and reproducible high content screening of live and fixed cells using Dye Drop," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Smriti Chawla & Anja Rockstroh & Melanie Lehman & Ellca Ratther & Atishay Jain & Anuneet Anand & Apoorva Gupta & Namrata Bhattacharya & Sarita Poonia & Priyadarshini Rai & Nirjhar Das & Angshul Majumd, 2022. "Gene expression based inference of cancer drug sensitivity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Adrià Fernández-Torras & Miquel Duran-Frigola & Martino Bertoni & Martina Locatelli & Patrick Aloy, 2022. "Integrating and formatting biomedical data as pre-calculated knowledge graph embeddings in the Bioteque," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Jurica Levatić & Marina Salvadores & Francisco Fuster-Tormo & Fran Supek, 2022. "Mutational signatures are markers of drug sensitivity of cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    5. Seungyeul Yoo & Abhilasha Sinha & Dawei Yang & Nasser K. Altorki & Radhika Tandon & Wenhui Wang & Deebly Chavez & Eunjee Lee & Ayushi S. Patel & Takashi Sato & Ranran Kong & Bisen Ding & Eric E. Schad, 2022. "Integrative network analysis of early-stage lung adenocarcinoma identifies aurora kinase inhibition as interceptor of invasion and progression," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Alon Stern & Mariam Fokra & Boris Sarvin & Ahmad Abed Alrahem & Won Dong Lee & Elina Aizenshtein & Nikita Sarvin & Tomer Shlomi, 2023. "Inferring mitochondrial and cytosolic metabolism by coupling isotope tracing and deconvolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    8. Sayantani Ghosh Dastidar & Bony Kumar & Bo Lauckner & Damien Parrello & Danielle Perley & Maria Vlasenok & Antariksh Tyagi & Nii Koney-Kwaku Koney & Ata Abbas & Sergei Nechaev, 2023. "Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    9. Sumana Srivatsa & Hesam Montazeri & Gaia Bianco & Mairene Coto-Llerena & Mattia Marinucci & Charlotte K. Y. Ng & Salvatore Piscuoglio & Niko Beerenwinkel, 2022. "Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Cemal Erdem & Sean M. Gross & Laura M. Heiser & Marc R. Birtwistle, 2023. "MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Guidantonio Malagoli Tagliazucchi & Anna J. Wiecek & Eloise Withnell & Maria Secrier, 2023. "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    12. Souleymane Abdoul-Azize & Rihab Hami & Gaetan Riou & Céline Derambure & Camille Charbonnier & Jean-Pierre Vannier & Monica L. Guzman & Pascale Schneider & Olivier Boyer, 2024. "Glucocorticoids paradoxically promote steroid resistance in B cell acute lymphoblastic leukemia through CXCR4/PLC signaling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    13. Philip East & Gavin P. Kelly & Dhruva Biswas & Michela Marani & David C. Hancock & Todd Creasy & Kris Sachsenmeier & Charles Swanton & Julian Downward & Sophie de Carné Trécesson, 2022. "RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    14. Caterina Bartolacci & Cristina Andreani & Gonçalo Vale & Stefano Berto & Margherita Melegari & Anna Colleen Crouch & Dodge L. Baluya & George Kemble & Kurt Hodges & Jacqueline Starrett & Katerina Poli, 2022. "Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    15. Sanju Sinha & Karina Barbosa & Kuoyuan Cheng & Mark D. M. Leiserson & Prashant Jain & Anagha Deshpande & David M. Wilson & Bríd M. Ryan & Ji Luo & Ze’ev A. Ronai & Joo Sang Lee & Aniruddha J. Deshpand, 2021. "A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    16. Carolin Ector & Christoph Schmal & Jeff Didier & Sébastien De Landtsheer & Anna-Marie Finger & Francesca Müller-Marquardt & Johannes H. Schulte & Thomas Sauter & Ulrich Keilholz & Hanspeter Herzel & A, 2024. "Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    17. Zheqi Li & Olivia McGinn & Yang Wu & Amir Bahreini & Nolan M. Priedigkeit & Kai Ding & Sayali Onkar & Caleb Lampenfeld & Carol A. Sartorius & Lori Miller & Margaret Rosenzweig & Ofir Cohen & Nikhil Wa, 2022. "ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    18. Bingzhen Chen & Wenjuan Zhai & Lingchen Kong, 2022. "Variable selection and collinearity processing for multivariate data via row-elastic-net regularization," AStA Advances in Statistical Analysis, Springer;German Statistical Society, vol. 106(1), pages 79-96, March.
    19. Hao Wang & R. Alejandro Sica & Gurbakhash Kaur & Phillip M. Galbo & Zhixin Jing & Christopher D. Nishimura & Xiaoxin Ren & Ankit Tanwar & Bijan Etemad-Gilbertson & Britta Will & Deyou Zheng & David Fo, 2024. "TMIGD2 is an orchestrator and therapeutic target on human acute myeloid leukemia stem cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    20. Ozge Saatci & Metin Cetin & Meral Uner & Unal Metin Tokat & Ioulia Chatzistamou & Pelin Gulizar Ersan & Elodie Montaudon & Aytekin Akyol & Sercan Aksoy & Aysegul Uner & Elisabetta Marangoni & Mathew S, 2023. "Toxic PARP trapping upon cAMP-induced DNA damage reinstates the efficacy of endocrine therapy and CDK4/6 inhibitors in treatment-refractory ER+ breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30449-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.