{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:58:24Z","timestamp":1787497104777,"version":"build-2736575974"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T00:00:00Z","timestamp":1479081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T00:00:00Z","timestamp":1479081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In many cancers, the establishment of a patient\u2019s future treatment regime often relies on histopathological assessment of tumor tissue specimens in order to determine the extent of the \u2018pathological response\u2019 to a given therapy. However, histopathological assessment of pathological response remains subjective. Here we use MALDI mass spectrometry imaging to generate lipid signatures from colorectal cancer liver metastasis specimens resected from patients preoperatively treated with chemotherapy. Using these signatures we obtained a unique pathological response score that correlates with prognosis. In addition, we identify single lipid moieties that are overexpressed in different histopathological features of the tumor, which have potential as new biomarkers for assessing response to therapy. These data show that computational methods, focusing on the lipidome, can be used to determine prognostic markers for response to chemotherapy and may potentially improve risk assessment and patient care.<\/jats:p>","DOI":"10.1038\/srep36814","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T05:20:09Z","timestamp":1479100809000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Assessment of pathological response to therapy using lipid mass spectrometry imaging"],"prefix":"10.1038","volume":"6","author":[{"given":"Nathan Heath","family":"Patterson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balqis","family":"Alabdulkarim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthoula","family":"Lazaris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieczyslaw M.","family":"Marcinkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu-hua","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"Vermeulen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chaurand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Metrakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,14]]},"reference":[{"key":"BFsrep36814_CR1","first-page":"104","volume":"64","author":"R Siegel","year":"2014","unstructured":"Siegel, R., Desantis, C. & Jemal, A. Colorectal cancer statistics. CA: a cancer journal for clinicians 64, 104\u2013117 (2014).","journal-title":"CA: a cancer journal for clinicians"},{"key":"BFsrep36814_CR2","first-page":"1161","volume":"20","author":"N Kemeny","year":"2006","unstructured":"Kemeny, N. Management of liver metastases from colorectal cancer. Oncology 20, 1161\u20131176, 1179; discussion 1179\u20131180, 1185\u20131166 (2006).","journal-title":"Oncology"},{"key":"BFsrep36814_CR3","doi-asserted-by":"publisher","first-page":"207","DOI":"10.4251\/wjgo.v5.i12.207","volume":"5","author":"G Spolverato","year":"2013","unstructured":"Spolverato, G., Ejaz, A., Azad, N. & Pawlik, T. M. Surgery for colorectal liver metastases: The evolution of determining prognosis. World journal of gastrointestinal oncology 5, 207\u2013221 (2013).","journal-title":"World journal of gastrointestinal oncology"},{"key":"BFsrep36814_CR4","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1097\/01.sla.0000145964.08365.01","volume":"240","author":"R Adam","year":"2004","unstructured":"Adam, R. et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Annals of surgery 240, 644\u2013657, discussion 657\u2013648 (2004).","journal-title":"Annals of surgery"},{"key":"BFsrep36814_CR5","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1177\/1758834013485111","volume":"5","author":"S Haraldsdottir","year":"2013","unstructured":"Haraldsdottir, S., Wu, C., Bloomston, M. & Goldberg, R. M. What is the optimal neo-adjuvant treatment for liver metastasis? Therapeutic advances in medical oncology 5, 221\u2013234 (2013).","journal-title":"Therapeutic advances in medical oncology"},{"key":"BFsrep36814_CR6","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1245\/s10434-006-9105-x","volume":"13","author":"ZZ Hamady","year":"2006","unstructured":"Hamady, Z. Z. et al. Hepatic resection for colorectal metastasis: impact of tumour size. Annals of surgical oncology 13, 1493\u20131499 (2006).","journal-title":"Annals of surgical oncology"},{"key":"BFsrep36814_CR7","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1002\/bjs.1800780711","volume":"78","author":"R Doci","year":"1991","unstructured":"Doci, R. et al. One hundred patients with hepatic metastases from colorectal cancer treated by resection: analysis of prognostic determinants. The British journal of surgery 78, 797\u2013801 (1991).","journal-title":"The British journal of surgery"},{"key":"BFsrep36814_CR8","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1007\/s00534-002-0754-2","volume":"11","author":"N Kokudo","year":"2004","unstructured":"Kokudo, N. et al. Surgery for multiple hepatic colorectal metastases. Journal of hepato-biliary-pancreatic surgery 11, 84\u201391 (2004).","journal-title":"Journal of hepato-biliary-pancreatic surgery"},{"key":"BFsrep36814_CR9","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1097\/00000658-200206000-00002","volume":"235","author":"MA Choti","year":"2002","unstructured":"Choti, M. A. et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Annals of surgery 235, 759\u2013766 (2002).","journal-title":"Annals of surgery"},{"key":"BFsrep36814_CR10","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.jamcollsurg.2009.12.041","volume":"210","author":"H Nathan","year":"2010","unstructured":"Nathan, H. et al. Conditional survival after surgical resection of colorectal liver metastasis: an international multi-institutional analysis of 949 patients. Journal of the American College of Surgeons 210, 755\u2013764, 764\u2013756 (2010).","journal-title":"Journal of the American College of Surgeons"},{"key":"BFsrep36814_CR11","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1245\/s10434-011-1819-8","volume":"18","author":"N Ayez","year":"2011","unstructured":"Ayez, N. et al. Is the clinical risk score for patients with colorectal liver metastases still useable in the era of effective neoadjuvant chemotherapy? Annals of surgical oncology 18, 2757\u20132763 (2011).","journal-title":"Annals of surgical oncology"},{"key":"BFsrep36814_CR12","doi-asserted-by":"publisher","first-page":"e49442","DOI":"10.1371\/journal.pone.0049442","volume":"7","author":"N Snoeren","year":"2012","unstructured":"Snoeren, N. et al. Exploring gene expression signatures for predicting disease free survival after resection of colorectal cancer liver metastases. PloS one 7, e49442 (2012).","journal-title":"PloS one"},{"key":"BFsrep36814_CR13","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.bbrc.2015.01.064","volume":"458","author":"A Kogita","year":"2015","unstructured":"Kogita, A. et al. Inter- and intra-tumor profiling of multi-regional colon cancer and metastasis. Biochemical and biophysical research communications 458, 52\u201356 (2015).","journal-title":"Biochemical and biophysical research communications"},{"key":"BFsrep36814_CR14","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/jnci\/djr153","volume":"103","author":"FA Sinicrope","year":"2011","unstructured":"Sinicrope, F. A. et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. Journal of the National Cancer Institute 103, 863\u2013875 (2011).","journal-title":"Journal of the National Cancer Institute"},{"key":"BFsrep36814_CR15","doi-asserted-by":"publisher","first-page":"3992","DOI":"10.1158\/0008-5472.CAN-06-0191","volume":"66","author":"A Li\u00e8vre","year":"2006","unstructured":"Li\u00e8vre, A. et al. KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer. Cancer Research 66, 3992\u20133995 (2006).","journal-title":"Cancer Research"},{"key":"BFsrep36814_CR16","doi-asserted-by":"publisher","first-page":"4983","DOI":"10.1200\/JCO.2006.05.8156","volume":"24","author":"T Aloia","year":"2006","unstructured":"Aloia, T. et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 24, 4983\u20134990 (2006).","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"key":"BFsrep36814_CR17","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/S1470-2045(09)70064-6","volume":"10","author":"YS Chun","year":"2009","unstructured":"Chun, Y. S., Laurent, A., Maru, D. & Vauthey, J. N. Management of chemotherapy-associated hepatotoxicity in colorectal liver metastases. The Lancet. Oncology 10, 278\u2013286 (2009).","journal-title":"The Lancet. Oncology"},{"key":"BFsrep36814_CR18","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1200\/JCO.2007.13.7471","volume":"26","author":"R Adam","year":"2008","unstructured":"Adam, R. et al. Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? Journal of clinical oncology: official journal of the American Society of Clinical Oncology 26, 1635\u20131641 (2008).","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"key":"BFsrep36814_CR19","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1097\/SLA.0b013e3181b0c6e4","volume":"250","author":"K Tanaka","year":"2009","unstructured":"Tanaka, K. et al. Importance of complete pathologic response to prehepatectomy chemotherapy in treating colorectal cancer metastases. Annals of surgery 250, 935\u2013942 (2009).","journal-title":"Annals of surgery"},{"key":"BFsrep36814_CR20","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1093\/annonc\/mdl386","volume":"18","author":"L Rubbia-Brandt","year":"2007","unstructured":"Rubbia-Brandt, L. et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Annals of oncology: official journal of the European Society for Medical Oncology\/ESMO 18, 299\u2013304 (2007).","journal-title":"Annals of oncology: official journal of the European Society for Medical Oncology\/ESMO"},{"key":"BFsrep36814_CR21","doi-asserted-by":"publisher","first-page":"5344","DOI":"10.1200\/JCO.2008.17.5299","volume":"26","author":"DG Blazer 3rd","year":"2008","unstructured":"Blazer, D. G. 3rd et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 26, 5344\u20135351 (2008).","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"key":"BFsrep36814_CR22","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/j.1477-2574.2010.00170.x","volume":"12","author":"G Chan","year":"2010","unstructured":"Chan, G. et al. Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy. HPB: the official journal of the International Hepato Pancreato Biliary Association 12, 277\u2013284 (2010).","journal-title":"HPB: the official journal of the International Hepato Pancreato Biliary Association"},{"key":"BFsrep36814_CR23","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1097\/PAS.0b013e31824057e7","volume":"36","author":"HH Chang","year":"2012","unstructured":"Chang, H. H., Leeper, W. R., Chan, G., Quan, D. & Driman, D. K. Infarct-like necrosis: a distinct form of necrosis seen in colorectal carcinoma liver metastases treated with perioperative chemotherapy. The American journal of surgical pathology 36, 570\u2013576 (2012).","journal-title":"The American journal of surgical pathology"},{"key":"BFsrep36814_CR24","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/j.urology.2010.08.031","volume":"77","author":"GJ Netto","year":"2011","unstructured":"Netto, G. J., Eisenberger, M., Epstein, J. I. & Investigators, T.A.X.T. Interobserver variability in histologic evaluation of radical prostatectomy between central and local pathologists: findings of TAX 3501 multinational clinical trial. Urology 77, 1155\u20131160 (2011).","journal-title":"Urology"},{"key":"BFsrep36814_CR25","doi-asserted-by":"publisher","first-page":"30","DOI":"10.4103\/2153-3539.120747","volume":"4","author":"G Lozanski","year":"2013","unstructured":"Lozanski, G. et al. Inter-reader variability in follicular lymphoma grading: Conventional and digital reading. Journal of pathology informatics 4, 30 (2013).","journal-title":"Journal of pathology informatics"},{"key":"BFsrep36814_CR26","doi-asserted-by":"publisher","first-page":"4883","DOI":"10.1016\/j.jprot.2012.04.005","volume":"75","author":"P Chaurand","year":"2012","unstructured":"Chaurand, P. Imaging mass spectrometry of thin tissue sections: a decade of collective efforts. Journal of proteomics 75, 4883\u20134892 (2012).","journal-title":"Journal of proteomics"},{"key":"BFsrep36814_CR27","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/86573","volume":"7","author":"M Stoeckli","year":"2001","unstructured":"Stoeckli, M., Chaurand, P., Hallahan, D. E. & Caprioli, R. M. Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nature medicine 7, 493\u2013496 (2001).","journal-title":"Nature medicine"},{"key":"BFsrep36814_CR28","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/nmeth1094","volume":"4","author":"DS Cornett","year":"2007","unstructured":"Cornett, D. S., Reyzer, M. L., Chaurand, P. & Caprioli, R. M. MALDI imaging mass spectrometry: molecular snapshots of biochemical systems. Nature methods 4, 828\u2013833 (2007).","journal-title":"Nature methods"},{"key":"BFsrep36814_CR29","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/nrc2917","volume":"10","author":"K Schwamborn","year":"2010","unstructured":"Schwamborn, K. & Caprioli, R. M. Molecular imaging by mass spectrometry\u2013looking beyond classical histology. Nature reviews. Cancer 10, 639\u2013646 (2010).","journal-title":"Nature reviews. Cancer"},{"key":"BFsrep36814_CR30","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1021\/cr3004295","volume":"113","author":"JL Norris","year":"2013","unstructured":"Norris, J. L. & Caprioli, R. M. Analysis of tissue specimens by matrix-assisted laser desorption\/ionization imaging mass spectrometry in biological and clinical research. Chemical reviews 113, 2309\u20132342 (2013).","journal-title":"Chemical reviews"},{"key":"BFsrep36814_CR31","doi-asserted-by":"publisher","first-page":"3237","DOI":"10.1021\/cr100012c","volume":"110","author":"K Chughtai","year":"2010","unstructured":"Chughtai, K. & Heeren, R. M. Mass spectrometric imaging for biomedical tissue analysis. Chemical reviews 110, 3237\u20133277 (2010).","journal-title":"Chemical reviews"},{"key":"BFsrep36814_CR32","doi-asserted-by":"publisher","first-page":"2860","DOI":"10.1021\/ac3034294","volume":"85","author":"A Thomas","year":"2013","unstructured":"Thomas, A. et al. Histology-driven data mining of lipid signatures from multiple imaging mass spectrometry analyses: application to human colorectal cancer liver metastasis biopsies. Analytical chemistry 85, 2860\u20132866 (2013).","journal-title":"Analytical chemistry"},{"key":"BFsrep36814_CR33","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1002\/pmic.201300434","volume":"14","author":"EE Jones","year":"2014","unstructured":"Jones, E. E. et al. MALDI imaging mass spectrometry profiling of proteins and lipids in clear cell renal cell carcinoma. Proteomics 14, 924\u2013935 (2014).","journal-title":"Proteomics"},{"key":"BFsrep36814_CR34","doi-asserted-by":"publisher","first-page":"9012","DOI":"10.1158\/0008-5472.CAN-10-0360","volume":"70","author":"ER Amstalden van Hove","year":"2010","unstructured":"Amstalden van Hove, E. R. et al. Multimodal mass spectrometric imaging of small molecules reveals distinct spatio-molecular signatures in differentially metastatic breast tumor models. Cancer Res 70, 9012\u20139021 (2010).","journal-title":"Cancer Res"},{"key":"BFsrep36814_CR35","doi-asserted-by":"publisher","first-page":"24560","DOI":"10.3390\/ijms141224560","volume":"14","author":"J Cimino","year":"2013","unstructured":"Cimino, J. et al. Towards lipidomics of low-abundant species for exploring tumor heterogeneity guided by high-resolution mass spectrometry imaging. International journal of molecular sciences 14, 24560\u201324580 (2013).","journal-title":"International journal of molecular sciences"},{"key":"BFsrep36814_CR36","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1186\/1471-2105-13-S16-S11","volume":"13","author":"T Alexandrov","year":"2012","unstructured":"Alexandrov, T. MALDI imaging mass spectrometry: statistical data analysis and current computational challenges. BMC bioinformatics 13 Suppl 16, S11 (2012).","journal-title":"BMC bioinformatics"},{"key":"BFsrep36814_CR37","doi-asserted-by":"publisher","first-page":"4962","DOI":"10.1016\/j.jprot.2012.06.014","volume":"75","author":"EA Jones","year":"2012","unstructured":"Jones, E. A., Deininger, S. O., Hogendoorn, P. C., Deelder, A. M. & McDonnell, L. A. Imaging mass spectrometry statistical analysis. Journal of proteomics 75, 4962\u20134989 (2012).","journal-title":"Journal of proteomics"},{"key":"BFsrep36814_CR38","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1073\/pnas.1310524111","volume":"111","author":"KA Veselkov","year":"2014","unstructured":"Veselkov, K. A. et al. Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer. Proceedings of the National Academy of Sciences of the United States of America 111, 1216\u20131221 (2014).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep36814_CR39","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s12253-014-9803-9","volume":"21","author":"K Dede","year":"2015","unstructured":"Dede, K., Salamon, F., Landherr, L., Jakab, F. & Bursics, A. Pathologic assessment of response to chemotherapy in colorectal cancer liver metastases after hepatic resection: which method to use? Pathology oncology research: POR 21, 173\u2013179 (2015).","journal-title":"Pathology oncology research: POR"},{"key":"BFsrep36814_CR40","doi-asserted-by":"publisher","first-page":"4357","DOI":"10.1007\/s00216-014-7846-0","volume":"406","author":"S Guo","year":"2014","unstructured":"Guo, S. et al. Tissue imaging and serum lipidomic profiling for screening potential biomarkers of thyroid tumors by matrix-assisted laser desorption\/ionization-Fourier transform ion cyclotron resonance mass spectrometry. Analytical and bioanalytical chemistry 406, 4357\u20134370 (2014).","journal-title":"Analytical and bioanalytical chemistry"},{"key":"BFsrep36814_CR41","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1476-511X-9-15","volume":"9","author":"L Arana","year":"2010","unstructured":"Arana, L., Gangoiti, P., Ouro, A., Trueba, M. & Gomez-Munoz, A. Ceramide and ceramide 1-phosphate in health and disease. Lipids in health and disease 9, 15 (2010).","journal-title":"Lipids in health and disease"},{"key":"BFsrep36814_CR42","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/nrc1411","volume":"4","author":"B Ogretmen","year":"2004","unstructured":"Ogretmen, B. & Hannun, Y. A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nature reviews. Cancer 4, 604\u2013616 (2004).","journal-title":"Nature reviews. Cancer"},{"key":"BFsrep36814_CR43","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1194\/jlr.M300158-JLR200","volume":"45","author":"A Gomez-Munoz","year":"2004","unstructured":"Gomez-Munoz, A., Kong, J. Y., Salh, B. & Steinbrecher, U. P. Ceramide-1-phosphate blocks apoptosis through inhibition of acid sphingomyelinase in macrophages. Journal of lipid research 45, 99\u2013105 (2004).","journal-title":"Journal of lipid research"},{"key":"BFsrep36814_CR44","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.chemphyslip.2011.04.010","volume":"164","author":"CD Magnusson","year":"2011","unstructured":"Magnusson, C. D. & Haraldsson, G. G. Ether lipids. Chemistry and physics of lipids 164, 315\u2013340 (2011).","journal-title":"Chemistry and physics of lipids"},{"key":"BFsrep36814_CR45","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1021\/ac2033547","volume":"84","author":"A Thomas","year":"2012","unstructured":"Thomas, A., Charbonneau, J. L., Fournaise, E. & Chaurand, P. Sublimation of new matrix candidates for high spatial resolution imaging mass spectrometry of lipids: enhanced information in both positive and negative polarities after 1,5-diaminonapthalene deposition. Analytical chemistry 84, 2048\u20132054 (2012).","journal-title":"Analytical chemistry"},{"key":"BFsrep36814_CR46","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1136\/jcp.25.2.123","volume":"25","author":"MI Filipe","year":"1972","unstructured":"Filipe, M. I. The value of a study of the mucosubstances in rectal biopsies from patients with carcinoma of the rectum and lower sigmoid in the diagnosis of premalignant mucosa. Journal of clinical pathology 25, 123\u2013128 (1972).","journal-title":"Journal of clinical pathology"},{"key":"BFsrep36814_CR47","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1007\/BF02050423","volume":"40","author":"S Kyzer","year":"1997","unstructured":"Kyzer, S. & Gordon, P. H. Determination of proliferative activity in colorectal carcinoma using monoclonal antibody Ki67. Diseases of the colon and rectum 40, 322\u2013325 (1997).","journal-title":"Diseases of the colon and rectum"},{"key":"BFsrep36814_CR48","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/S1044-0305(03)00064-3","volume":"14","author":"FF Hsu","year":"2003","unstructured":"Hsu, F. F. & Turk, J. Electrospray ionization\/tandem quadrupole mass spectrometric studies on phosphatidylcholines: the fragmentation processes. Journal of the American Society for Mass Spectrometry 14, 352\u2013363 (2003).","journal-title":"Journal of the American Society for Mass Spectrometry"},{"key":"BFsrep36814_CR49","doi-asserted-by":"publisher","first-page":"W606","DOI":"10.1093\/nar\/gkm324","volume":"35","author":"E Fahy","year":"2007","unstructured":"Fahy, E., Sud, M., Cotter, D. & Subramaniam, S. LIPID MAPS online tools for lipid research. Nucleic acids research 35, W606\u2013W612 (2007).","journal-title":"Nucleic acids research"},{"key":"BFsrep36814_CR50","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/978-1-60761-987-1_12","volume":"696","author":"A Rompp","year":"2011","unstructured":"Rompp, A. et al. imzML: Imaging Mass Spectrometry Markup Language: A common data format for mass spectrometry imaging. Methods in molecular biology 696, 205\u2013224 (2011).","journal-title":"Methods in molecular biology"},{"key":"BFsrep36814_CR51","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1093\/bioinformatics\/bts447","volume":"28","author":"S Gibb","year":"2012","unstructured":"Gibb, S. & Strimmer, K. MALDIquant: a versatile R package for the analysis of mass spectrometry data. Bioinformatics 28, 2270\u20132271 (2012).","journal-title":"Bioinformatics"},{"key":"BFsrep36814_CR52","doi-asserted-by":"publisher","first-page":"i230","DOI":"10.1093\/bioinformatics\/btr246","volume":"27","author":"T Alexandrov","year":"2011","unstructured":"Alexandrov, T. & Kobarg, J. H. Efficient spatial segmentation of large imaging mass spectrometry datasets with spatially aware clustering. Bioinformatics 27, i230\u2013i238 (2011).","journal-title":"Bioinformatics"},{"key":"BFsrep36814_CR53","doi-asserted-by":"crossref","unstructured":"Bemis, K. D. et al. Cardinal: an R package for statistical analysis of mass spectrometry-based imaging experiments. Bioinformatics (2015).","DOI":"10.1093\/bioinformatics\/btv146"},{"key":"BFsrep36814_CR54","doi-asserted-by":"publisher","first-page":"2855","DOI":"10.1093\/bioinformatics\/btp515","volume":"25","author":"KA Le Cao","year":"2009","unstructured":"Le Cao, K. A., Gonzalez, I. & Dejean, S. integrOmics: an R package to unravel relationships between two omics datasets. Bioinformatics 25, 2855\u20132856 (2009).","journal-title":"Bioinformatics"},{"key":"BFsrep36814_CR55","doi-asserted-by":"publisher","first-page":"3940","DOI":"10.1093\/bioinformatics\/bti623","volume":"21","author":"T Sing","year":"2005","unstructured":"Sing, T., Sander, O., Beerenwinkel, N. & Lengauer, T. ROCR: visualizing classifier performance in R. Bioinformatics 21, 3940\u20133941 (2005).","journal-title":"Bioinformatics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep36814.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36814","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36814.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T19:20:11Z","timestamp":1672860011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep36814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,14]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep36814"],"URL":"https:\/\/doi.org\/10.1038\/srep36814","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,14]]},"assertion":[{"value":"29 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36814"}}