Machine Learning analysis of high-grade serous ovarian cancer proteomic dataset reveals novel candidate biomarkers.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
23 02 2022
Historique:
received: 02 08 2021
accepted: 02 02 2022
entrez: 24 2 2022
pubmed: 25 2 2022
medline: 23 3 2022
Statut: epublish

Résumé

Ovarian cancer is one of the most common gynecological malignancies, ranking third after cervical and uterine cancer. High-grade serous ovarian cancer (HGSOC) is one of the most aggressive subtype, and the late onset of its symptoms leads in most cases to an unfavourable prognosis. Current predictive algorithms used to estimate the risk of having Ovarian Cancer fail to provide sufficient sensitivity and specificity to be used widely in clinical practice. The use of additional biomarkers or parameters such as age or menopausal status to overcome these issues showed only weak improvements. It is necessary to identify novel molecular signatures and the development of new predictive algorithms able to support the diagnosis of HGSOC, and at the same time, deepen the understanding of this elusive disease, with the final goal of improving patient survival. Here, we apply a Machine Learning-based pipeline to an open-source HGSOC Proteomic dataset to develop a decision support system (DSS) that displayed high discerning ability on a dataset of HGSOC biopsies. The proposed DSS consists of a double-step feature selection and a decision tree, with the resulting output consisting of a combination of three highly discriminating proteins: TOP1, PDIA4, and OGN, that could be of interest for further clinical and experimental validation. Furthermore, we took advantage of the ranked list of proteins generated during the feature selection steps to perform a pathway analysis to provide a snapshot of the main deregulated pathways of HGSOC. The datasets used for this study are available in the Clinical Proteomic Tumor Analysis Consortium (CPTAC) data portal ( https://cptac-data-portal.georgetown.edu/ ).

Identifiants

pubmed: 35197484
doi: 10.1038/s41598-022-06788-2
pii: 10.1038/s41598-022-06788-2
pmc: PMC8866540
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3041

Informations de copyright

© 2022. The Author(s).

Références

Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2016. CA A Cancer J. Clin. 66, 7–30 (2016).
doi: 10.3322/caac.21332
Webb, P. M. & Jordan, S. J. Epidemiology of epithelial ovarian cancer. Best Pract. Res. Clin. Obstet. Gynaecol. 41, 3–14 (2017).
pubmed: 27743768 doi: 10.1016/j.bpobgyn.2016.08.006
Cook, D. P. & Vanderhyden, B. C. Ovarian cancer and the evolution of subtype classifications using transcriptional profiling. Biol. Reprod. 101, 645–658 (2019).
pubmed: 31187121 doi: 10.1093/biolre/ioz099
Kossaï, M., Leary, A., Scoazec, J.-Y. & Genestie, C. Ovarian cancer: A heterogeneous disease. Pathobiology 85, 41–49 (2018).
pubmed: 29020678 doi: 10.1159/000479006
Matulonis, U. A. et al. Ovarian cancer. Nat. Rev. Dis. Prim. 2, 1–22 (2016).
Rosen, D. G. et al. Potential markers that complement expression of ca125 in epithelial ovarian cancer. Gynecol. Oncol. 99, 267–277 (2005).
pubmed: 16061277 doi: 10.1016/j.ygyno.2005.06.040
Torre, L. A. et al. Ovarian cancer statistics, 2018. CA A Cancer J. Clin. 68, 284–296 (2018).
doi: 10.3322/caac.21456
Aune, G., Torp, S. H., Syversen, U., Hagen, B., & Tingulstad, S. Ten years’ experience with centralized surgery of ovarian cancer in one health region in Norway. Int J Gynecol Cancer. 22(2) (2012).
Earle, C. C. et al. Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients. J. Natl. Cancer Inst. 98, 172–180 (2006).
pubmed: 16449677 doi: 10.1093/jnci/djj019
Giede, K. C., Kieser, K., Dodge, J. & Rosen, B. Who should operate on patients with ovarian cancer? An evidence-based review. Gynecol. Oncol. 99, 447–461 (2005).
pubmed: 16126262 doi: 10.1016/j.ygyno.2005.07.008
Bast, R. et al. Reactivity of a monoclonal antibody with human ovarian carcinoma. J. Clin. Investig. 68, 1331–1337 (1981).
pubmed: 7028788 pmcid: 370929 doi: 10.1172/JCI110380
Hellström, I. et al. The he4 (wfdc2) protein is a biomarker for ovarian carcinoma. Cancer Res. 63, 3695–3700 (2003).
pubmed: 12839961
Kim, J.-H. et al. Osteopontin as a potential diagnostic biomarker for ovarian cancer. JAMA 287, 1671–1679 (2002).
pubmed: 11926891 doi: 10.1001/jama.287.13.1671
Jacobs, I. et al. A risk of malignancy index incorporating ca 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. BJOG Int. J. Obstet. Gynaecol. 97, 922–929 (1990).
doi: 10.1111/j.1471-0528.1990.tb02448.x
Moore, R. G. et al. A novel multiple marker bioassay utilizing he4 and ca125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol. Oncol. 112, 40–46 (2009).
pubmed: 18851871 doi: 10.1016/j.ygyno.2008.08.031
Zhang, Z. & Chan, D. W. The road from discovery to clinical diagnostics: Lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers. Cancer Epidemiol. Prev. Biomark. 19, 2995–2999 (2010).
doi: 10.1158/1055-9965.EPI-10-0580
Moore, R. G. et al. Multiple biomarker algorithms to predict epithelial ovarian cancer in women with a pelvic mass: Can additional makers improve performance?. Gynecol. Oncol. 154, 150–155 (2019).
pubmed: 30992143 pmcid: 6666425 doi: 10.1016/j.ygyno.2019.04.006
Yang, W.-L., Lu, Z. & Bast, R. C. Jr. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev. Mol. Diagn. 17, 577–591 (2017).
pubmed: 28468520 pmcid: 5823503 doi: 10.1080/14737159.2017.1326820
Hamed, E. O. et al. Significance of he4 estimation in comparison with ca125 in diagnosis of ovarian cancer and assessment of treatment response. Diagn. Pathol. 8, 11 (2013).
pubmed: 23343214 pmcid: 3621278 doi: 10.1186/1746-1596-8-11
Buamah, P. Benign conditions associated with raised serum ca-125 concentration. J. Surg. Oncol. 75, 264–265 (2000).
pubmed: 11135268 doi: 10.1002/1096-9098(200012)75:4<264::AID-JSO7>3.0.CO;2-Q
Muinao, T., Boruah, H. P. D. & Pal, M. Diagnostic and prognostic biomarkers in ovarian cancer and the potential roles of cancer stem cells—An updated review. Exp. Cell Res. 362, 1–10 (2018).
pubmed: 29079264 doi: 10.1016/j.yexcr.2017.10.018
Muinao, T., Boruah, H. P. D. & Pal, M. Multi-biomarker panel signature as the key to diagnosis of ovarian cancer. Heliyon 5, e02826 (2019).
pubmed: 31867451 pmcid: 6906658 doi: 10.1016/j.heliyon.2019.e02826
Karlsen, M. A. et al. Evaluation of he4, ca125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass. Gynecol. Oncol. 127, 379–383 (2012).
pubmed: 22835718 doi: 10.1016/j.ygyno.2012.07.106
(NCI/NIH), C. P. T. A. C. Cptac Ovarian Cancer Confirmatory Study (2021).
Boehm, A. M., Pütz, S., Altenhöfer, D., Sickmann, A. & Falk, M. Precise protein quantification based on peptide quantification using itraq™. BMC Bioinform. 8, 1–18 (2007).
doi: 10.1186/1471-2105-8-214
Zhang, H. et al. Integrated proteogenomic characterization of human high-grade serous ovarian cancer. Cell 166, 755–765 (2016).
pubmed: 27372738 pmcid: 4967013 doi: 10.1016/j.cell.2016.05.069
Kononenko, I. Estimating attributes: Analysis and extensions of relief. In European Conference on Machine Learning 171–182 (Springer, 1994).
Breiman, L., Friedman, J., Stone, C. J. & Olshen, R. A. Classification and Regression Trees (CRC Press, 1984).
Subramanian, A. et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. 102, 15545–15550 (2005).
pubmed: 16199517 pmcid: 1239896 doi: 10.1073/pnas.0506580102
Mootha, V. K. et al. Pgc-1[Formula: see text]-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273 (2003).
pubmed: 12808457 doi: 10.1038/ng1180
Shannon, P. et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).
pubmed: 14597658 pmcid: 403769 doi: 10.1101/gr.1239303
Reimand, J. et al. Pathway enrichment analysis and visualization of omics data using g: Profiler, gsea, cytoscape and enrichmentmap. Nat. Protocols 14, 482–517 (2019).
pubmed: 30664679 doi: 10.1038/s41596-018-0103-9
Hegde, P. S., White, I. R. & Debouck, C. Interplay of transcriptomics and proteomics. Curr. Opin. Biotechnol. 14, 647–651 (2003).
pubmed: 14662396 doi: 10.1016/j.copbio.2003.10.006
Vogel, C. & Marcotte, E. M. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat. Rev. Genet. 13, 227–232 (2012).
pubmed: 22411467 pmcid: 3654667 doi: 10.1038/nrg3185
Tegge, A. N., Caldwell, C. W. & Xu, D. Pathway correlation profile of gene-gene co-expression for identifying pathway perturbation. PLoS One 7, e52127 (2012).
pubmed: 23284898 pmcid: 3527387 doi: 10.1371/journal.pone.0052127
Johnson, D. G. & Schneider-Broussard, R. Role of e2f in cell cycle control and cancer. Front. Biosci. 3, d447–d448 (1998).
pubmed: 9556498 doi: 10.2741/A291
Dang, C. V. Myc on the path to cancer. Cell 149, 22–35 (2012).
pubmed: 22464321 pmcid: 3345192 doi: 10.1016/j.cell.2012.03.003
Kaur, G., Balasubramaniam, S. D., Lee, Y. J., Balakrishnan, V. & Oon, C. E. Minichromosome maintenance complex (mcm) genes profiling and mcm2 protein expression in cervical cancer development. Asian Pac. J. Cancer Prev. APJCP 20, 3043 (2019).
pubmed: 31653153 doi: 10.31557/APJCP.2019.20.10.3043
Cheng H, Zhang N, Pati D. Cohesin subunit RAD21: From biology to disease. Gene. 758, 144966 (2020).
pubmed: 32687945 pmcid: 7949736 doi: 10.1016/j.gene.2020.144966
Kanopka, A. Cell survival: Interplay between hypoxia and pre-mrna splicing. Exp. Cell Res. 356, 187–191 (2017).
pubmed: 28315669 doi: 10.1016/j.yexcr.2017.03.018
Qi, F. et al. Significance of alternative splicing in cancer cells. Chin. Med. J. 133, 221 (2020).
pubmed: 31764175 pmcid: 7028187 doi: 10.1097/CM9.0000000000000542
Hautbergue G. M. RNA Nuclear Export: From Neurological Disorders to Cancer. Adv Exp Med Biol. 1007, 89–109 (2017).
pubmed: 28840554 doi: 10.1007/978-3-319-60733-7_6
Wu, K., He, J., Pu, W. & Peng, Y. The role of exportin-5 in microrna biogenesis and cancer. Genom. Proteom. Bioinform. 16, 120–126 (2018).
doi: 10.1016/j.gpb.2017.09.004
Azizian, N. G. & Li, Y. Xpo1-dependent nuclear export as a target for cancer therapy. J. Hematol. Oncol. 13, 1–9 (2020).
doi: 10.1186/s13045-020-00903-4
Ruggero, D. Translational control in cancer etiology. Cold Spring Harbor Perspect. Biol. 5, a012336 (2013).
doi: 10.1101/cshperspect.a012336
Nupponen, N. N. et al. Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer. Am. J. Pathol. 154, 1777–1783 (1999).
pubmed: 10362802 pmcid: 1866614 doi: 10.1016/S0002-9440(10)65433-8
Saramäki, O. et al. Amplification of eif3s3 gene is associated with advanced stage in prostate cancer. Am. J. Pathol. 159, 2089–2094 (2001).
pubmed: 11733359 pmcid: 1850612 doi: 10.1016/S0002-9440(10)63060-X
Belin, S. et al. Dysregulation of ribosome biogenesis and translational capacity is associated with tumor progression of human breast cancer cells. PLoS One 4, e7147 (2009).
pubmed: 19779612 pmcid: 2744998 doi: 10.1371/journal.pone.0007147
Popp, M.W.-L. & Maquat, L. E. Organizing principles of mammalian nonsense-mediated mRNA decay. Annu. Rev. Genet. 47, 139–165 (2013).
pubmed: 24274751 pmcid: 4148824 doi: 10.1146/annurev-genet-111212-133424
Moriarty, P. M., Reddy, C. C. & Maquat, L. E. Selenium deficiency reduces the abundance of mRNA for se-dependent glutathione peroxidase 1 by a UGA-dependent mechanism likely to be nonsense codon-mediated decay of cytoplasmic mRNA. Mol. Cell. Biol. 18, 2932–2939 (1998).
pubmed: 9566912 pmcid: 110672 doi: 10.1128/MCB.18.5.2932
Hatfield, D. L., Tsuji, P. A., Carlson, B. A. & Gladyshev, V. N. Selenium and selenocysteine: Roles in cancer, health, and development. Trends Biochem. Sci. 39, 112–120 (2014).
pubmed: 24485058 pmcid: 3943681 doi: 10.1016/j.tibs.2013.12.007
Short, S. P. & Williams, C. S. Selenoproteins in tumorigenesis and cancer progression. Adv. Cancer Res. 136, 49–83 (2017).
pubmed: 29054422 pmcid: 5819884 doi: 10.1016/bs.acr.2017.08.002
Ballard, M. S. & Hinck, L. A roundabout way to cancer. Adv. Cancer Res. 114, 187–235 (2012).
pubmed: 22588058 pmcid: 4121377 doi: 10.1016/B978-0-12-386503-8.00005-3
Tong, M., Jun, T., Nie, Y., Hao, J. & Fan, D. The role of the slit/robo signaling pathway. J. Cancer 10, 2694 (2019).
pubmed: 31258778 pmcid: 6584916 doi: 10.7150/jca.31877
Anastasiadou, E. et al. Mir-200c-3p contrasts pd-l1 induction by combinatorial therapies and slows proliferation of epithelial ovarian cancer through downregulation of [Formula: see text]-catenin and c-myc. Cells 10, 519 (2021).
pubmed: 33804458 pmcid: 7998372 doi: 10.3390/cells10030519
Mold, C., Nemerow, G., Bradt, B. & Cooper, N. Cr2 is a complement activator and the covalent binding site for c3 during alternative pathway activation by Raji cells. J. Immunol. 140, 1923–1929 (1988).
pubmed: 2831273
Janiszewska, M., Primi, M. C. & Izard, T. Cell adhesion in cancer: Beyond the migration of single cells. J. Biol. Chem. 295, 2495–2505 (2020).
pubmed: 31937589 pmcid: 7039572 doi: 10.1074/jbc.REV119.007759
Schwartz, M. A. & Assoian, R. K. Integrins and cell proliferation: Regulation of cyclin-dependent kinases via cytoplasmic signaling pathways. J. Cell Sci. 114, 2553–2560 (2001).
pubmed: 11683383 doi: 10.1242/jcs.114.14.2553
Turk, B., Turk, D. & Turk, V. Protease signalling: The cutting edge. EMBO J. 31, 1630–1643 (2012).
pubmed: 22367392 pmcid: 3321211 doi: 10.1038/emboj.2012.42
Zheng, D., Chen, H., Davids, J., Bryant, M. & Lucas, A. Serpins for diagnosis and therapy in cancer. Cardiovasc. Haematol. Disord. Drug Targets Former. Curr. Drug Targets Cardiovasc. Hematol. Disord. 13, 123–132 (2013).
Baek, J. Y. et al. Serpin b5 is a cea-interacting biomarker for colorectal cancer. Int. J. Cancer 134, 1595–1604 (2014).
pubmed: 24114705 doi: 10.1002/ijc.28494
Vycital, O. et al. Expression of serpin b9 as a prognostic factor of colorectal cancer. Anticancer Res. 39, 6063–6066 (2019).
pubmed: 31704833 doi: 10.21873/anticanres.13813
van Sluis, G. L., Büller, H. R. & Spek, C. A. The role of activated protein c in cancer progression. Thromb. Res. 125, S138–S142 (2010).
pubmed: 20433994 doi: 10.1016/S0049-3848(10)70032-3
Spek, C. A. & Arruda, V. R. The protein c pathway in cancer metastasis. Thromb. Res. 129, S80–S84 (2012).
pubmed: 22682140 doi: 10.1016/S0049-3848(12)70022-1
Nierodzik, M. et al. Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo. J. Clin. Investig. 87, 229–236 (1991).
pubmed: 1845869 pmcid: 295033 doi: 10.1172/JCI114976
Schmidt, W. M. et al. DNA damage, somatic aneuploidy, and malignant sarcoma susceptibility in muscular dystrophies. PLoS Genet. 7, e1002042 (2011).
pubmed: 21533183 pmcid: 3077392 doi: 10.1371/journal.pgen.1002042
Jones, L., Naidoo, M., Machado, L. R. & Anthony, K. The Duchenne muscular dystrophy gene and cancer. Cell. Oncol. 44, 1–14 (2020).
Hauser, A. S., Attwood, M. M., Rask-Andersen, M., Schiöth, H. B. & Gloriam, D. E. Trends in GPCR drug discovery: New agents, targets and indications. Nat. Rev. Drug Discov. 16, 829–842 (2017).
pubmed: 29075003 pmcid: 6882681 doi: 10.1038/nrd.2017.178
Wu, V. et al. Illuminating the onco-gpcrome: Novel g protein-coupled receptor-driven oncocrine networks and targets for cancer immunotherapy. J. Biol. Chem. 294, 11062–11086 (2019).
pubmed: 31171722 pmcid: 6643028 doi: 10.1074/jbc.REV119.005601
Bjornsti, M.-A. & Kaufmann, S. H. Topoisomerases and cancer chemotherapy: Recent advances and unanswered questions. F1000Research 8 (2019).
Husain, A. et al. Chromatin remodeller smarca4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability. Nat. Commun. 7, 1–15 (2016).
doi: 10.1038/ncomms10549
Miao, Z.-H. et al. Nonclassic functions of human topoisomerase I: Genome-wide and pharmacologic analyses. Cancer Res. 67, 8752–8761 (2007).
pubmed: 17875716 doi: 10.1158/0008-5472.CAN-06-4554
Pommier, Y., Sun, Y., Shar-yin, N. H. & Nitiss, J. L. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nat. Rev. Mol. Cell Biol. 17, 703 (2016).
pubmed: 27649880 doi: 10.1038/nrm.2016.111
Thomas, A. & Pommier, Y. Targeting topoisomerase I in the era of precision medicine. Clin. Cancer Res. 25, 6581–6589 (2019).
pubmed: 31227499 pmcid: 6858945 doi: 10.1158/1078-0432.CCR-19-1089
Peaper, D. R. & Cresswell, P. Regulation of MHC class I assembly and peptide binding. Annu. Rev. Cell Dev. Biol. 24, 343–368 (2008).
pubmed: 18729726 doi: 10.1146/annurev.cellbio.24.110707.175347
Wang, Z., Zhang, H. & Cheng, Q. Pdia4: The basic characteristics, functions and its potential connection with cancer. Biomed. Pharmacother. 122, 109688 (2020).
pubmed: 31794946 doi: 10.1016/j.biopha.2019.109688
Samanta, S. et al. Expression of protein disulfide isomerase family members correlates with tumor progression and patient survival in ovarian cancer. Oncotarget 8, 103543 (2017).
pubmed: 29262583 pmcid: 5732749 doi: 10.18632/oncotarget.21569
Kuo, T.-F. et al. Protein disulfide isomerase a4 acts as a novel regulator of cancer growth through the procaspase pathway. Oncogene 36, 5484–5496 (2017).
pubmed: 28534513 doi: 10.1038/onc.2017.156
Tufo, G. et al. The protein disulfide isomerases pdia4 and pdia6 mediate resistance to cisplatin-induced cell death in lung adenocarcinoma. Cell Death Differ. 21, 685–695 (2014).
pubmed: 24464223 pmcid: 3978299 doi: 10.1038/cdd.2013.193
Deckx, S., Heymans, S. & Papageorgiou, A.-P. The diverse functions of osteoglycin: A deceitful dwarf, or a master regulator of disease?. FASEB J. 30, 2651–2661 (2016).
pubmed: 27080639 doi: 10.1096/fj.201500096R
Liang, X., Gao, J., Wang, Q., Hou, S. & Wu, C. Ecrg4 represses cell proliferation and invasiveness via nfic/ogn/nf-[Formula: see text]b signaling pathway in bladder cancer. Front. Genet. 11, 846 (2020).
pubmed: 32922434 pmcid: 7456849 doi: 10.3389/fgene.2020.00846
Xu, T. et al. Osteoglycin (ogn) inhibits cell proliferation and invasiveness in breast cancer via pi3k/akt/mtor signaling pathway. OncoTargets Ther. 12, 10639 (2019).
doi: 10.2147/OTT.S222967
Husain, I., Mohler, J. L., Seigler, H. F. & Besterman, J. M. Elevation of topoisomerase I messenger RNA, protein, and catalytic activity in human tumors: Demonstration of tumor-type specificity and implications for cancer chemotherapy. Cancer Res. 54, 539–546 (1994).
pubmed: 8275492
Liu, L.-M. et al. DNA topoisomerase 1 and 2a function as oncogenes in liver cancer and may be direct targets of nitidine chloride. Int. J. Oncol. 53, 1897–1912 (2018).
pubmed: 30132517 pmcid: 6192772
Ogino, M. et al. Implications of topoisomerase (top1 and top2[Formula: see text]) expression in patients with breast cancer. In Vivo 34, 3483–3487 (2020).
pubmed: 33144457 pmcid: 7811623 doi: 10.21873/invivo.12188
Boonsong, A. et al. Topoisomerase I protein expression in primary colorectal cancer and lymph node metastases. Hum. Pathol. 33, 1114–1119 (2002).
pubmed: 12454816 doi: 10.1053/hupa.2002.129202
Gilbert, D., Chalmers, A. & El-Khamisy, S. Topoisomerase I inhibition in colorectal cancer: Biomarkers and therapeutic targets. Br. J. Cancer 106, 18–24 (2012).
pubmed: 22108516 doi: 10.1038/bjc.2011.498
Xu, Y. & Her, C. Inhibition of topoisomerase (DNA) I (top1): DNA damage repair and anticancer therapy. Biomolecules 5, 1652–1670 (2015).
pubmed: 26287259 pmcid: 4598769 doi: 10.3390/biom5031652

Auteurs

Federica Farinella (F)

Division of Clinical Pathology, Laboratori Vita s.r.l., Via Sabaudia 19, 04100, Latina, Italy.

Mario Merone (M)

Unit of Computer Systems an Bioinformatics, Department of Engineering, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128, Rome, Italy. m.merone@unicampus.it.

Luca Bacco (L)

Unit of Computer Systems an Bioinformatics, Department of Engineering, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128, Rome, Italy.
ItaliaNLP Lab, Istituto di Linguistica Computazionale "Antonio Zampolli", National Research Council, Via Giuseppe Moruzzi, 1, 56124, Pisa, Italy.
Webmonks s.r.l., Via del Triopio, 5, 00178, Rome, Italy.

Adriano Capirchio (A)

Computational and Translational Neuroscience Laboratory, Institute of Cognitive Sciences and Technologies, National Research Council (CTN-ISTC-CNR), Via San Martino della Battaglia 44, 00185, Rome, Italy.
AI2Life s.r.l., Innovative Start-Up, ISTC-CNR Spin-Off, Via Sebino 32, 00199, Rome, Italy.

Massimo Ciccozzi (M)

Unit of Medical Statistic and Epidemiology, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128, Rome, Italy.

Daniele Caligiore (D)

Computational and Translational Neuroscience Laboratory, Institute of Cognitive Sciences and Technologies, National Research Council (CTN-ISTC-CNR), Via San Martino della Battaglia 44, 00185, Rome, Italy.
AI2Life s.r.l., Innovative Start-Up, ISTC-CNR Spin-Off, Via Sebino 32, 00199, Rome, Italy.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH