scholarly journals Evaluation of colorectal cancer subtypes and cell lines using deep learning

2019 ◽  
Vol 2 (6) ◽  
pp. e201900517 ◽  
Author(s):  
Jonathan Ronen ◽  
Sikander Hayat ◽  
Altuna Akalin

Colorectal cancer (CRC) is a common cancer with a high mortality rate and a rising incidence rate in the developed world. Molecular profiling techniques have been used to better understand the variability between tumors and disease models such as cell lines. To maximize the translatability and clinical relevance of in vitro studies, the selection of optimal cancer models is imperative. We have developed a deep learning–based method to measure the similarity between CRC tumors and disease models such as cancer cell lines. Our method efficiently leverages multiomics data sets containing copy number alterations, gene expression, and point mutations and learns latent factors that describe data in lower dimensions. These latent factors represent the patterns that are clinically relevant and explain the variability of molecular profiles across tumors and cell lines. Using these, we propose refined CRC subtypes and provide best-matching cell lines to different subtypes. These findings are relevant to patient stratification and selection of cell lines for early-stage drug discovery pipelines, biomarker discovery, and target identification.

2018 ◽  
Author(s):  
Jonathan Ronen ◽  
Sikander Hayat ◽  
Altuna Akalin

ABSTRACTColorectal cancer (CRC) is a common cancer with a high mortality rate and a rising incidence rate in the developed world. The disease shows variable drug response and outcome. Molecular profiling techniques have been used to better understand the variability between tumours as well as cancer models such as cell lines. Drug discovery programs use cell lines as a proxy for human cancers to characterize their molecular makeup and drug response, identify relevant indications and discover biomarkers. In order to maximize the translatability and the clinical relevance of in vitro studies, selection of optimal cancer models is imperative. We have developed a deep learning based method to measure the similarity between CRC tumors and other tumors or disease models such as cancer cell lines. Our method efficiently leverages multi-omics data sets containing copy number alterations, gene expression and point mutations, and learns latent factors that describe the data in lower dimension. These latent factors represent the patterns across gene expression, copy number, and mutational profiles which are clinically relevant and explain the variability of molecular profiles across tumours and cell lines. Using these, we propose a refined colorectal cancer sample classification and provide best-matching cell lines in terms of multi-omics for the different subtypes. These findings are relevant for patient stratification and selection of cell lines for early stage drug discovery pipelines, biomarker discovery, and target identification.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karianne Giller Fleten ◽  
J. Johannes Eksteen ◽  
Brynjar Mauseth ◽  
Ketil André Camilio ◽  
Terje Vasskog ◽  
...  

AbstractOncolytic peptides represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities, including colorectal cancer (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, a feature of particular interest in non-immunogenic CRC. Oncolytic peptides DTT-205 and DTT-304 were administered by intratumoral injection in subcutaneous tumors established from murine CRC cell lines CT26 and MC38, and complete regression was obtained in the majority of animals. When cured animals were rechallenged by splenic injection of tumor cells, 1/23 animals developed liver metastases, compared to 19/22 naïve animals. Treatment with both peptides was well tolerated, but monitoring post-injection hemodynamic parameters in rats, less extensive changes were observed with DTT-205 than DTT-304, favoring DTT-205 for future drug development. DTT-205 was subsequently shown to have strong in vitro activity in a panel of 33 cancer cell lines. In conclusion, both peptides exerted a strong inhibitory effect in two immunocompetent CRC models and induced a systemic effect preventing development of liver metastases upon splenic rechallenge. If a similar effect could be obtained in humans, these drugs would be of particular interest for combinatory treatment with immune checkpoint inhibitors in metastatic CRC.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Dennis Wang ◽  
James Hensman ◽  
Ginte Kutkaite ◽  
Tzen S Toh ◽  
Ana Galhoz ◽  
...  

High-throughput testing of drugs across molecular-characterised cell lines can identify candidate treatments and discover biomarkers. However, the cells’ response to a drug is typically quantified by a summary statistic from a best-fit dose-response curve, whilst neglecting the uncertainty of the curve fit and the potential variability in the raw readouts. Here, we model the experimental variance using Gaussian Processes, and subsequently, leverage uncertainty estimates to identify associated biomarkers with a new Bayesian framework. Applied to in vitro screening data on 265 compounds across 1074 cancer cell lines, our models identified 24 clinically established drug-response biomarkers, and provided evidence for six novel biomarkers by accounting for association with low uncertainty. We validated our uncertainty estimates with an additional drug screen of 26 drugs, 10 cell lines with 8 to 9 replicates. Our method is applicable to any dose-response data without replicates, and improves biomarker discovery for precision medicine.


2014 ◽  
Vol 13 (2) ◽  
pp. 251-261 ◽  
Author(s):  
Dmitry A. Ovchinnikov ◽  
Drew M. Titmarsh ◽  
Patrick R.J. Fortuna ◽  
Alejandro Hidalgo ◽  
Samah Alharbi ◽  
...  

2021 ◽  
Vol 1 (19) ◽  
pp. 194-196
Author(s):  
O.F Kandarakov ◽  
A.V. Bruter ◽  
A.V. Petrovskaya ◽  
A.V. Belyavsky

The possibility of using HA- and FLAG–tags embedded into CD52 surface protein for magnetic separation of transduced cells in vitro was investigated. The efficiency of selection of transfected cell lines, both with single and binary tags, was shown to exceed 85%. Thus, surface markers on the basis of CD52 protein with integrated HA- and FLAG-tags are applicable for cell selection by the MACS method.


2011 ◽  
Vol 317 (14) ◽  
pp. 2019-2030 ◽  
Author(s):  
Yoshitaka Yamaguchi ◽  
Atsushi Takayanagi ◽  
Jiabing Chen ◽  
Kosuke Sakai ◽  
Jun Kudoh ◽  
...  

2003 ◽  
Vol 3 (1) ◽  
pp. 49-52 ◽  
Author(s):  
MALEE NANAKORN ◽  
WALAIKARN JIAMJETJAROON ◽  
SRISOM SUWANAWONG ◽  
CHALERMCHAI WONGWATTANA ◽  
IE SUNG SHIM

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