{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:56:51Z","timestamp":1792108611890,"version":"4.4.0"},"reference-count":48,"publisher":"American Chemical Society (ACS)","issue":"4","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["DP7OD020317"],"award-info":[{"award-number":["DP7OD020317"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R44GM122196-02A1"],"award-info":[{"award-number":["R44GM122196-02A1"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R43NS107079-01"],"award-info":[{"award-number":["1R43NS107079-01"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["3R43NS107079-01S1"],"award-info":[{"award-number":["3R43NS107079-01S1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rare diseases impact hundreds of millions of individuals worldwide. However, few therapies exist to treat the rare disease population because financial resources are limited, the number of patients affected is low, bioactivity data is often nonexistent, and very few animal models exist to support preclinical development efforts. Sialidosis is an ultrarare lysosomal storage disorder in which mutations in the NEU1 gene result in the deficiency of the lysosomal enzyme sialidase-1. This enzyme catalyzes the removal of sialic acid moieties from glycoproteins and glycolipids. Therefore, the defective or deficient protein leads to the buildup of sialylated glycoproteins as well as several characteristic symptoms of sialidosis including visual impairment, ataxia, hepatomegaly, dysostosis multiplex, and developmental delay. In this study, we used a bibliometric tool to generate links between lysosomal storage disease (LSD) targets and existing bioactivity data that could be curated in order to build machine learning models and screen compounds in silico. We focused on sialidase as an example, and we used the data curated from the literature to build a Bayesian model which was then used to score compound libraries and rank these molecules for in vitro testing. Two compounds were identified from in vitro testing using microscale thermophoresis, namely sulfameter (Kd 2.15 \u00b1 1.02 \u03bcM) and mexenone (Kd 8.88 \u00b1 4.02 \u03bcM), which validated our approach to identifying new molecules binding to this protein, which could represent possible drug candidates that can be evaluated further as potential chaperones for this ultrarare lysosomal disease for which there is currently no treatment. Combining bibliometric and machine learning approaches has the ability to assist in curating small molecule data and model building, respectively, for rare disease drug discovery. This approach also has the capability to identify new compounds that are potential drug candidates.<\/jats:p>","DOI":"10.1021\/acsomega.0c05591","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T15:53:03Z","timestamp":1611157983000},"page":"3186-3193","source":"Crossref","is-referenced-by-count":14,"title":["Using Bibliometric Analysis and Machine Learning to\nIdentify Compounds Binding to Sialidase-1"],"prefix":"10.1021","volume":"6","author":[{"given":"Jennifer J.","family":"Klein","sequence":"first","affiliation":[{"name":"Collaborations Pharmaceuticals, Inc. , 840 Main Campus Drive, Lab 3510 , , ,","place":["Raleigh, North Carolina, United States, 27606"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy C.","family":"Baker","sequence":"additional","affiliation":[{"name":"ParlezChem , 123 W Union Street , , ,","place":["Hillsborough, North Carolina, United States, 27278"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Foil","sequence":"additional","affiliation":[{"name":"Collaborations Pharmaceuticals, Inc. , 840 Main Campus Drive, Lab 3510 , , ,","place":["Raleigh, North Carolina, United States, 27606"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley M.","family":"Zorn","sequence":"additional","affiliation":[{"name":"Collaborations Pharmaceuticals, Inc. , 840 Main Campus Drive, Lab 3510 , , ,","place":["Raleigh, North Carolina, United States, 27606"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Urbina","sequence":"additional","affiliation":[{"name":"Collaborations Pharmaceuticals, Inc. , 840 Main Campus Drive, Lab 3510 , , ,","place":["Raleigh, North Carolina, United States, 27606"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1456-8882","authenticated-orcid":true,"given":"Ana C.","family":"Puhl","sequence":"additional","affiliation":[{"name":"Collaborations Pharmaceuticals, Inc. , 840 Main Campus Drive, Lab 3510 , , ,","place":["Raleigh, North Carolina, United States, 27606"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5691-5790","authenticated-orcid":true,"given":"Sean","family":"Ekins","sequence":"additional","affiliation":[{"name":"Collaborations Pharmaceuticals, Inc. , 840 Main Campus Drive, Lab 3510 , , ,","place":["Raleigh, North Carolina, United States, 27606"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"2026090317491842000_cit1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41431-019-0508-0","article-title":"Estimating cumulative point prevalence of rare diseases: analysis\nof the Orphanet database","volume":"28","author":"Nguengang Wakap","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"2026090317491842000_cit2","doi-asserted-by":"publisher","first-page":"jcs221739","DOI":"10.1242\/jcs.221739","article-title":"Lysosomal storage disorders\n- challenges, concepts\nand avenues for therapy: beyond rare diseases","volume":"132","author":"Marques","year":"2019","journal-title":"J. Cell Sci."},{"key":"2026090317491842000_cit3","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1111\/jpc.13122","article-title":"Lysosomal\nstorage disorders: A review of the musculoskeletal features","volume":"52","author":"James","year":"2016","journal-title":"J. Paediatr. Child Health"},{"key":"2026090317491842000_cit4","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41572-018-0037-0","article-title":"Lysosomal\nstorage diseases","volume":"4","author":"Platt","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"2026090317491842000_cit5","first-page":"87","article-title":"Update on treatment of lysosomal storage diseases","volume":"26","author":"Bruni","year":"2007","journal-title":"Acta Myol."},{"key":"2026090317491842000_cit6","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.jcyt.2015.03.609","article-title":"Cord blood is the optimal graft source for the treatment\nof pediatric patients with lysosomal storage diseases: clinical outcomes\nand future directions","volume":"17","author":"Aldenhoven","year":"2015","journal-title":"Cytotherapy"},{"key":"2026090317491842000_cit7","first-page":"547","article-title":"Receptor-mediated\nuptake of lysosomal enzymes","volume":"23","author":"Sly","year":"1978","journal-title":"Prog. Clin. Biol.\nRes."},{"key":"2026090317491842000_cit8","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.ymthe.2006.01.006","article-title":"Gene therapy for\nlysosomal storage diseases","volume":"13","author":"Sands","year":"2006","journal-title":"Mol. Ther."},{"key":"2026090317491842000_cit9","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/j.1651-2227.2008.00660.x","article-title":"CNS-directed gene\ntherapy for lysosomal storage diseases","volume":"97","author":"Sands","year":"2008","journal-title":"Acta\nPaediatr."},{"key":"2026090317491842000_cit10","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41573-019-0059-7","article-title":"Publisher Correction:\nTherapies for rare diseases: therapeutic modalities, progress and\nchallenges ahead","volume":"19","author":"Tambuyzer","year":"2020","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026090317491842000_cit11","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1517\/21678707.2015.1025746","article-title":"Pathogenesis,\nEmerging therapeutic\ntargets and Treatment in Sialidosis","volume":"3","author":"D\u2019Azzo","year":"2015","journal-title":"Expert\nOpin. Orphan Drugs"},{"key":"2026090317491842000_cit12","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1684\/epd.2016.0845","article-title":"Sialidoses","volume":"18","author":"Franceschetti","year":"2016","journal-title":"Epileptic Disord."},{"key":"2026090317491842000_cit13","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/humu.10268","article-title":"Molecular\npathology of NEU1 gene\nin sialidosis","volume":"22","author":"Seyrantepe","year":"2003","journal-title":"Hum. Mutat."},{"key":"2026090317491842000_cit14","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1096\/fj.03-0941fje","article-title":"Targeting macrophages with baculovirus-produced\nlysosomal enzymes: implications for enzyme replacement therapy of\nthe glycoprotein storage disorder galactosialidosis","volume":"18","author":"Bonten","year":"2004","journal-title":"FASEB J."},{"key":"2026090317491842000_cit15","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.ymgme.2005.03.007","article-title":"Short-term,\nhigh dose enzyme replacement therapy in sialidosis mice","volume":"85","author":"Wang","year":"2005","journal-title":"Mol. Genet. Metab."},{"key":"2026090317491842000_cit16","doi-asserted-by":"publisher","first-page":"11261","DOI":"10.1021\/acs.jmedchem.8b01411","article-title":"Selective Inhibitors\nof Human Neuraminidase 1 (NEU1)","volume":"61","author":"Guo","year":"2018","journal-title":"J. Med. Chem."},{"key":"2026090317491842000_cit17","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/mt.2011.227","article-title":"Preclinical\ndose-finding study with a liver-tropic, recombinant AAV-2\/8 vector\nin the mouse model of galactosialidosis","volume":"20","author":"Hu","year":"2012","journal-title":"Mol.\nTher."},{"key":"2026090317491842000_cit18","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/s41563-019-0338-z","article-title":"Exploiting machine\nlearning for end-to-end drug discovery and development","volume":"18","author":"Ekins","year":"2019","journal-title":"Nat. Mater."},{"key":"2026090317491842000_cit19","unstructured":"Anon.\n          . 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Agents Chemother."},{"key":"2026090317491842000_cit28","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1111\/j.1365-2133.1975.tb03103.x","article-title":"A study of chemical light screening agents","volume":"92","author":"Macleod","year":"1975","journal-title":"Br. J. Dermatol."},{"key":"2026090317491842000_cit29","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.bbagen.2009.01.006","article-title":"Protective protein\/cathepsin A rescues\nN-glycosylation\ndefects in neuraminidase-1","volume":"1790","author":"Wang","year":"2009","journal-title":"Biochim. Biophys.\nActa"},{"key":"2026090317491842000_cit30","first-page":"31","article-title":"Inhibition\nof cytochrome C oxidase by glutathione in vitro","volume":"25","author":"Gullner","year":"1990","journal-title":"Acta Biochim. Biophys. Hung."},{"key":"2026090317491842000_cit31","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3390\/diagnostics8020029","article-title":"Sialidosis: A Review of Morphology and Molecular Biology of a Rare\nPediatric Disorder","volume":"8","author":"Khan","year":"2018","journal-title":"Diagnostics"},{"key":"2026090317491842000_cit32","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1002\/mgg3.262","article-title":"A comprehensive global genotype-phenotype\ndatabase for rare diseases","volume":"5","author":"Trujillano","year":"2017","journal-title":"Mol. Genet. Genomic\nMed."},{"key":"2026090317491842000_cit33","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1007\/s11606-014-2908-8","article-title":"RD-Connect:\nan integrated platform connecting databases, registries, biobanks\nand clinical bioinformatics for rare disease research","volume":"29","author":"Thompson","year":"2014","journal-title":"J. Gen. Intern. Med."},{"key":"2026090317491842000_cit34","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1002\/humu.22078","article-title":"Representation of rare\ndiseases in health information systems: the\nOrphanet approach to serve a wide range of end users","volume":"33","author":"Rath","year":"2012","journal-title":"Hum. Mutat."},{"key":"2026090317491842000_cit35","unstructured":"Anon.\n          . PubChem. https:\/\/pubchem.ncbi.nlm.nih.gov\/ (accessed 2019-03-25)."},{"key":"2026090317491842000_cit36","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1093\/bib\/bbr006","article-title":"Database identifies FDA-approved drugs with potential\nto be repurposed for treatment of orphan diseases","volume":"12","author":"Xu","year":"2011","journal-title":"Briefings Bioinf."},{"key":"2026090317491842000_cit37","unstructured":"Anon.\n          .  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