{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T10:12:56Z","timestamp":1793873576776,"version":"4.6.1"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-08578-8","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T16:37:09Z","timestamp":1754584629000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Machine learning-based proteomics profiling of ALS identifies downregulation of RPS29 that maintains protein homeostasis and STMN2 level"],"prefix":"10.1038","volume":"8","author":[{"given":"Wei","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yian","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihui","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-6710","authenticated-orcid":false,"given":"Tianlin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-119X","authenticated-orcid":false,"given":"Zhicheng","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-9209","authenticated-orcid":false,"given":"Bangbao","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-0298","authenticated-orcid":false,"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-8004","authenticated-orcid":false,"given":"Zhixin","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"8578_CR1","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","volume":"400","author":"EL Feldman","year":"2022","unstructured":"Feldman, E. L. et al. Amyotrophic lateral sclerosis.  Lancet 400, 1363\u20131380 (2022).","journal-title":"Lancet"},{"key":"8578_CR2","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/S1474-4422(18)30089-9","volume":"17","author":"H-J Westeneng","year":"2018","unstructured":"Westeneng, H.-J. et al. Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model. Lancet Neurol. 17, 423\u2013433 (2018).","journal-title":"Lancet Neurol."},{"key":"8578_CR3","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/nrneurol.2011.153","volume":"7","author":"O Hardiman","year":"2011","unstructured":"Hardiman, O., van den Berg, L. & Kiernan, M. Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat. Rev. Neurol. 7, 639\u2013649 (2011).","journal-title":"Nat. Rev. Neurol."},{"key":"8578_CR4","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/s41582-020-00434-z","volume":"17","author":"MC Kiernan","year":"2021","unstructured":"Kiernan, M. C. et al. Improving clinical trial outcomes in amyotrophic lateral sclerosis. Nat. Rev. Neurol. 17, 104\u2013118 (2021).","journal-title":"Nat. Rev. Neurol."},{"key":"8578_CR5","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1136\/jnnp.2010.224501","volume":"82","author":"S Byrne","year":"2011","unstructured":"Byrne, S. et al. Rate of familial amyotrophic lateral sclerosis: a systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry 82, 623\u2013627 (2011).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"8578_CR6","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41573-022-00612-2","volume":"22","author":"RJ Mead","year":"2023","unstructured":"Mead, R. J., Shan, N., Reiser, H. J., Marshall, F. & Shaw, P. J. Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation. Nat. Rev. Drug Discov. 22, 185\u2013212 (2023).","journal-title":"Nat. Rev. Drug Discov."},{"key":"8578_CR7","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13024-022-00593-1","volume":"18","author":"E Udine","year":"2023","unstructured":"Udine, E., Jain, A. & van Blitterswijk, M. Advances in sequencing technologies for amyotrophic lateral sclerosis research. Mol. Neurodegener. 18, 4 (2023).","journal-title":"Mol. Neurodegener."},{"key":"8578_CR8","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s10038-022-01055-8","volume":"68","author":"N Suzuki","year":"2023","unstructured":"Suzuki, N., Nishiyama, A., Warita, H. & Aoki, M. Genetics of amyotrophic lateral sclerosis: seeking therapeutic targets in the era of gene therapy. J. Hum. Genet. 68, 131\u2013152 (2023).","journal-title":"J. Hum. Genet."},{"key":"8578_CR9","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nature09320","volume":"466","author":"AC Elden","year":"2010","unstructured":"Elden, A. C. et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466, 1069\u20131075 (2010).","journal-title":"Nature"},{"key":"8578_CR10","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1126\/science.abq5622","volume":"379","author":"MW Baughn","year":"2023","unstructured":"Baughn, M. W. et al. Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science 379, 1140\u20131149 (2023).","journal-title":"Science"},{"key":"8578_CR11","doi-asserted-by":"publisher","first-page":"eadi5548","DOI":"10.1126\/sciadv.adi5548","volume":"9","author":"JR Mann","year":"2023","unstructured":"Mann, J. R. et al. Loss of function of the ALS-associated NEK1 kinase disrupts microtubule homeostasis and nuclear import. Sci. Adv. 9, eadi5548 (2023).","journal-title":"Sci. Adv."},{"key":"8578_CR12","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","volume":"387","author":"TM Miller","year":"2022","unstructured":"Miller, T. M. et al. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N. Engl. J. Med. 387, 1099\u20131110 (2022).","journal-title":"N. Engl. J. Med"},{"key":"8578_CR13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.stem.2021.12.008","volume":"29","author":"E Giacomelli","year":"2022","unstructured":"Giacomelli, E. et al. Human stem cell models of neurodegeneration: from basic science of amyotrophic lateral sclerosis to clinical translation. Cell Stem Cell 29, 11\u201335 (2022).","journal-title":"Cell Stem Cell"},{"key":"8578_CR14","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1016\/j.neuron.2023.01.010","volume":"111","author":"MJ Workman","year":"2023","unstructured":"Workman, M. J. et al. Large-scale differentiation of iPSC-derived motor neurons from ALS and control subjects. Neuron 111, 1191\u20131204.e5 (2023).","journal-title":"Neuron"},{"key":"8578_CR15","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nm.4490","volume":"24","author":"Y Shi","year":"2018","unstructured":"Shi, Y. et al. Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS\/FTD human induced motor neurons. Nat. Med. 24, 313\u2013325 (2018).","journal-title":"Nat. Med."},{"key":"8578_CR16","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/j.neuron.2020.06.027","volume":"107","author":"AN Coyne","year":"2020","unstructured":"Coyne, A. N. et al. G4C2 repeat RNA initiates a POM121-mediated reduction in specific nucleoporins in C9orf72 ALS\/FTD. Neuron 107, 1124\u20131140.e11 (2020).","journal-title":"Neuron"},{"key":"8578_CR17","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.cmet.2021.01.005","volume":"33","author":"T Wang","year":"2021","unstructured":"Wang, T. et al. C9orf72 regulates energy homeostasis by stabilizing mitochondrial complex I assembly. Cell Metab. 33, 531\u2013546.e9 (2021).","journal-title":"Cell Metab."},{"key":"8578_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33079-1","volume":"13","author":"T Wang","year":"2022","unstructured":"Wang, T. et al. Intracellular energy controls dynamics of stress-induced ribonucleoprotein granules. Nat. Commun. 13, 5584 (2022).","journal-title":"Nat. Commun."},{"key":"8578_CR19","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/s41593-021-01006-0","volume":"25","author":"EG Baxi","year":"2022","unstructured":"Baxi, E. G. et al. Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines. Nat. Neurosci. 25, 226\u2013237 (2022).","journal-title":"Nat. Neurosci."},{"key":"8578_CR20","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s00441-023-03816-z","volume":"394","author":"S Ng","year":"2023","unstructured":"Ng, S., Masarone, S., Watson, D. & Barnes, M. R. The benefits and pitfalls of machine learning for biomarker discovery. Cell Tissue Res. 394, 17\u201331 (2023).","journal-title":"Cell Tissue Res."},{"key":"8578_CR21","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/978-1-4939-7704-8_25","volume":"1750","author":"R Li","year":"2018","unstructured":"Li, R. Data mining and machine learning methods for dementia research. Methods Mol. Biol. 1750, 363\u2013370 (2018).","journal-title":"Methods Mol. Biol."},{"key":"8578_CR22","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/nn.4273","volume":"19","author":"S Sances","year":"2016","unstructured":"Sances, S. et al. Modeling ALS with motor neurons derived from human induced pluripotent stem cells. Nat. Neurosci. 19, 542\u2013553 (2016).","journal-title":"Nat. Neurosci."},{"key":"8578_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113636","volume":"43","author":"AJ Guise","year":"2024","unstructured":"Guise, A. J. et al. TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis. Cell Rep. 43, 113636 (2024).","journal-title":"Cell Rep."},{"key":"8578_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23774-w","volume":"12","author":"T Wang","year":"2021","unstructured":"Wang, T. et al. MOGONET integrates multi-omics data using graph convolutional networks allowing patient classification and biomarker identification. Nat. Commun. 12, 3445 (2021).","journal-title":"Nat. Commun."},{"key":"8578_CR25","doi-asserted-by":"publisher","first-page":"2588","DOI":"10.1016\/j.molcel.2022.04.022","volume":"82","author":"H Shen","year":"2022","unstructured":"Shen, H. et al. Sexually dimorphic RNA helicases DDX3X and DDX3Y differentially regulate RNA metabolism through phase separation. Mol. Cell 82, 2588\u20132603.e9 (2022).","journal-title":"Mol. Cell"},{"key":"8578_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113219","volume":"327","author":"BA Harlan","year":"2020","unstructured":"Harlan, B. A. et al. Evaluation of the NAD+ biosynthetic pathway in ALS patients and effect of modulating NAD+ levels in hSOD1-linked ALS mouse models. Exp. Neurol. 327, 113219 (2020).","journal-title":"Exp. Neurol."},{"key":"8578_CR27","doi-asserted-by":"publisher","first-page":"823","DOI":"10.18632\/aging.101195","volume":"9","author":"P Andr\u00e9s-Benito","year":"2017","unstructured":"Andr\u00e9s-Benito, P., Moreno, J., Aso, E., Povedano, M. & Ferrer, I. Amyotrophic lateral sclerosis, gene deregulation in the anterior horn of the spinal cord and frontal cortex area 8: implications in frontotemporal lobar degeneration. Aging9, 823\u2013851 (2017).","journal-title":"Aging"},{"key":"8578_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44215-w","volume":"14","author":"ZS Chen","year":"2023","unstructured":"Chen, Z. S. et al. Mutant GGGGCC RNA prevents YY1 from binding to Fuzzy promoter which stimulates Wnt\/\u03b2-catenin pathway in C9ALS\/FTD. Nat. Commun. 14, 8420 (2023).","journal-title":"Nat. Commun."},{"key":"8578_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e24975","volume":"10","author":"C Harvey","year":"2024","unstructured":"Harvey, C. et al. Rare and common genetic determinants of mitochondrial function determine severity but not risk of amyotrophic lateral sclerosis. Heliyon 10, e24975 (2024).","journal-title":"Heliyon"},{"key":"8578_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112822","volume":"42","author":"J Park","year":"2023","unstructured":"Park, J. et al. Poly(GR) interacts with key stress granule factors promoting its assembly into cytoplasmic inclusions. Cell Rep. 42, 112822 (2023).","journal-title":"Cell Rep."},{"key":"8578_CR31","unstructured":"Lundberg, S. M. & Lee, S.-I. A unified approach to interpreting model predictions. In Proc. of the 31st International Conference on Neural Information Processing Systems 4768\u20134777 (Curran Associates Inc., 2017)."},{"key":"8578_CR32","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.neuron.2021.12.019","volume":"110","author":"S Zhang","year":"2022","unstructured":"Zhang, S. et al. Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis. Neuron 110, 992\u20131008.e11 (2022).","journal-title":"Neuron"},{"key":"8578_CR33","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.stem.2014.03.004","volume":"14","author":"E Kiskinis","year":"2014","unstructured":"Kiskinis, E. et al. Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1. Cell Stem Cell 14, 781\u2013795 (2014).","journal-title":"Cell Stem Cell"},{"key":"8578_CR34","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1038\/s41593-023-01374-9","volume":"26","author":"Y Li","year":"2023","unstructured":"Li, Y. et al. Globally reduced N6-methyladenosine (m6A) in C9ORF72-ALS\/FTD dysregulates RNA metabolism and contributes to neurodegeneration. Nat. Neurosci. 26, 1328\u20131338 (2023).","journal-title":"Nat. Neurosci."},{"key":"8578_CR35","doi-asserted-by":"publisher","first-page":"5707","DOI":"10.1007\/s00018-021-03872-0","volume":"78","author":"JR Kok","year":"2021","unstructured":"Kok, J. R., Palminha, N. M., Dos Santos Souza, C., El-Khamisy, S. F. & Ferraiuolo, L. DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity. Cell Mol. Life Sci. 78, 5707\u20135729 (2021).","journal-title":"Cell Mol. Life Sci."},{"key":"8578_CR36","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/s41593-018-0300-4","volume":"22","author":"JR Klim","year":"2019","unstructured":"Klim, J. R. et al. ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair. Nat. Neurosci. 22, 167\u2013179 (2019).","journal-title":"Nat. Neurosci."},{"key":"8578_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49196-y","volume":"15","author":"LC Gomes","year":"2024","unstructured":"Gomes, L. C. et al. Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target. Nat. Commun. 15, 4893 (2024).","journal-title":"Nat. Commun."},{"key":"8578_CR38","doi-asserted-by":"crossref","unstructured":"Larrea, D. Altered mitochondria-associated ER membrane (MAM) function shifts mitochondrial metabolism in amyotrophic lateral sclerosis (ALS). Nat. Commun. 16, 379 (2025).","DOI":"10.1038\/s41467-024-51578-1"},{"key":"8578_CR39","doi-asserted-by":"crossref","unstructured":"Lee, H. Multi-omic analysis of selectively vulnerable motor neuron subtypes implicates altered lipid metabolism in ALS. Nat. Neurosci. 24, 1673-1685 (2021).","DOI":"10.1038\/s41593-021-00944-z"},{"key":"8578_CR40","doi-asserted-by":"publisher","first-page":"e1001154","DOI":"10.1371\/journal.pgen.1001154","volume":"6","author":"N Huang","year":"2010","unstructured":"Huang, N., Lee, I., Marcotte, E. M. & Hurles, M. E. Characterising and predicting haploinsufficiency in the human genome. PLoS Genet. 6, e1001154 (2010).","journal-title":"PLoS Genet."},{"key":"8578_CR41","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1093\/bioinformatics\/btv602","volume":"33","author":"J Fadista","year":"2017","unstructured":"Fadista, J., Oskolkov, N., Hansson, O. & Groop, L. LoFtool: a gene intolerance score based on loss-of-function variants in 60,706 individuals. Bioinformatics 33, 471\u2013474 (2017).","journal-title":"Bioinformatics"},{"key":"8578_CR42","doi-asserted-by":"publisher","first-page":"e1003709","DOI":"10.1371\/journal.pgen.1003709","volume":"9","author":"S Petrovski","year":"2013","unstructured":"Petrovski, S., Wang, Q., Heinzen, E. L., Allen, A. S. & Goldstein, D. B. Genic intolerance to functional variation and the interpretation of personal genomes. PLoS Genet. 9, e1003709 (2013).","journal-title":"PLoS Genet."},{"key":"8578_CR43","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/j.celrep.2019.09.066","volume":"29","author":"OH Tam","year":"2019","unstructured":"Tam, O. H. et al. Postmortem cortex samples identify distinct molecular subtypes of ALS: retrotransposon activation, oxidative stress, and activated glia. Cell Rep. 29, 1164\u20131177.e5 (2019).","journal-title":"Cell Rep."},{"key":"8578_CR44","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1083\/jcb.201005117","volume":"190","author":"M-F O\u2019Donohue","year":"2010","unstructured":"O\u2019Donohue, M.-F., Choesmel, V., Faubladier, M., Fichant, G. & Gleizes, P.-E. Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits. J. Cell Biol. 190, 853\u2013866 (2010).","journal-title":"J. Cell Biol."},{"key":"8578_CR45","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1182\/blood-2013-11-540278","volume":"124","author":"L Mirabello","year":"2014","unstructured":"Mirabello, L. et al. Whole-exome sequencing and functional studies identify RPS29 as a novel gene mutated in multicase Diamond-Blackfan anemia families. Blood 124, 24\u201332 (2014).","journal-title":"Blood"},{"key":"8578_CR46","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.tig.2017.12.007","volume":"34","author":"M Kapur","year":"2018","unstructured":"Kapur, M. & Ackerman, S. L. mRNA translation gone awry: translation fidelity and neurological disease. Trends Genet. 34, 218\u2013231 (2018).","journal-title":"Trends Genet."},{"key":"8578_CR47","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.1016\/j.cmet.2021.08.017","volume":"33","author":"VE Martinez-Miguel","year":"2021","unstructured":"Martinez-Miguel, V. E. et al. Increased fidelity of protein synthesis extends lifespan. Cell Metab. 33, 2288\u20132300.e12 (2021).","journal-title":"Cell Metab."},{"key":"8578_CR48","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.jmb.2005.03.025","volume":"348","author":"J Salas-Marco","year":"2005","unstructured":"Salas-Marco, J. & Bedwell, D. M. Discrimination between defects in elongation fidelity and termination efficiency provides mechanistic insights into translational readthrough. J. Mol. Biol. 348, 801\u2013815 (2005).","journal-title":"J. Mol. Biol."},{"key":"8578_CR49","doi-asserted-by":"publisher","first-page":"6355","DOI":"10.1093\/nar\/gkad329","volume":"51","author":"R She","year":"2023","unstructured":"She, R., Luo, J. & Weissman, J. S. Translational fidelity screens in mammalian cells reveal eIF3 and eIF4G2 as regulators of start codon selectivity. Nucleic Acids Res. 51, 6355\u20136369 (2023).","journal-title":"Nucleic Acids Res."},{"key":"8578_CR50","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.cell.2020.12.025","volume":"184","author":"M Maor-Nof","year":"2021","unstructured":"Maor-Nof, M. et al. p53 is a central regulator driving neurodegeneration caused by C9orf72 poly(PR). Cell 184, 689\u2013708.e20 (2021).","journal-title":"Cell"},{"key":"8578_CR51","doi-asserted-by":"publisher","first-page":"2908","DOI":"10.1093\/brain\/awy241","volume":"141","author":"DA Solomon","year":"2018","unstructured":"Solomon, D. A. et al. A feedback loop between dipeptide-repeat protein, TDP-43, and karyopherin-\u03b1 mediates C9orf72-related neurodegeneration. Brain 141, 2908\u20132924 (2018).","journal-title":"Brain"},{"key":"8578_CR52","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1007\/s00401-021-02374-4","volume":"142","author":"S Diaz-Garcia","year":"2021","unstructured":"Diaz-Garcia, S. et al. Nuclear depletion of RNA-binding protein ELAVL3 (HuC) in sporadic and familial amyotrophic lateral sclerosis. Acta Neuropathol. 142, 985\u20131001 (2021).","journal-title":"Acta Neuropathol."},{"key":"8578_CR53","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1038\/s41588-021-00973-1","volume":"53","author":"W van Rheenen","year":"2021","unstructured":"van Rheenen, W. et al. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology. Nat. Genet. 53, 1636\u20131648 (2021).","journal-title":"Nat. Genet."},{"key":"8578_CR54","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.neuron.2018.02.027","volume":"97","author":"A Nicolas","year":"2018","unstructured":"Nicolas, A. et al. Genome-wide analyses identify KIF5A as a novel ALS gene. Neuron 97, 1268\u20131283.e6 (2018).","journal-title":"Neuron"},{"key":"8578_CR55","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1038\/ng.3622","volume":"48","author":"PARALS Registry","year":"2016","unstructured":"PARALS Registry et al. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat. Genet. 48, 1043\u20131048 (2016).","journal-title":"Nat. Genet."},{"key":"8578_CR56","doi-asserted-by":"publisher","first-page":"eabj0264","DOI":"10.1126\/scitranslmed.abj0264","volume":"14","author":"PJ Hop","year":"2022","unstructured":"Hop, P. J. et al. Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS. Sci. Transl. Med. 14, eabj0264 (2022).","journal-title":"Sci. Transl. Med."},{"key":"8578_CR57","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/S1474-4422(10)70184-8","volume":"9","author":"H Laaksovirta","year":"2010","unstructured":"Laaksovirta, H. et al. Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study. Lancet Neurol. 9, 978\u2013985 (2010).","journal-title":"Lancet Neurol."},{"key":"8578_CR58","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1038\/s41591-018-0140-5","volume":"24","author":"K Fujimori","year":"2018","unstructured":"Fujimori, K. et al. Modeling sporadic ALS in iPSC-derived motor neurons identifies a potential therapeutic agent. Nat. Med. 24, 1579\u20131589 (2018).","journal-title":"Nat. Med."},{"key":"8578_CR59","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.stem.2023.04.017","volume":"30","author":"S Morimoto","year":"2023","unstructured":"Morimoto, S. et al. Phase 1\/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery. Cell Stem Cell 30, 766\u2013780.e9 (2023).","journal-title":"Cell Stem Cell"},{"key":"8578_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37630-6","volume":"14","author":"OJ Ziff","year":"2023","unstructured":"Ziff, O. J. et al. Integrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology. Nat. Commun. 14, 2176 (2023).","journal-title":"Nat. Commun."},{"key":"8578_CR61","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.exphem.2011.11.007","volume":"40","author":"AM Taylor","year":"2012","unstructured":"Taylor, A. M. et al. Hematopoietic defects in rps29 mutant zebrafish depend upon p53 activation. Exp. Hematol. 40, 228\u2013237.e5 (2012).","journal-title":"Exp. Hematol."},{"key":"8578_CR62","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb5831","volume":"12","author":"A Taylor","year":"2020","unstructured":"Taylor, A. et al. Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia. Sci. Transl. Med. 12, eabb5831 (2020).","journal-title":"Sci. Transl. Med."},{"key":"8578_CR63","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111001","volume":"39","author":"KL Krus","year":"2022","unstructured":"Krus, K. L. et al. Loss of Stathmin-2, a hallmark of TDP-43-associated ALS, causes motor neuropathy. Cell Rep. 39, 111001 (2022).","journal-title":"Cell Rep."},{"key":"8578_CR64","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.tins.2021.02.008","volume":"44","author":"JR Klim","year":"2021","unstructured":"Klim, J. R., Pintacuda, G., Nash, L. A., Guerra San Juan, I. & Eggan, K. Connecting TDP-43 pathology with neuropathy. Trends Neurosci. 44, 424\u2013440 (2021).","journal-title":"Trends Neurosci."},{"key":"8578_CR65","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.ajhg.2021.03.011","volume":"108","author":"C Depienne","year":"2021","unstructured":"Depienne, C. & Mandel, J.-L. 30 years of repeat expansion disorders: What have we learned and what are the remaining challenges?. Am. J. Hum. Genet. 108, 764\u2013785 (2021).","journal-title":"Am. J. Hum. Genet."},{"key":"8578_CR66","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41580-021-00382-6","volume":"22","author":"I Malik","year":"2021","unstructured":"Malik, I., Kelley, C. P., Wang, E. T. & Todd, P. K. Molecular mechanisms underlying nucleotide repeat expansion disorders. Nat. Rev. Mol. Cell Biol. 22, 589\u2013607 (2021).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"8578_CR67","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1146\/annurev-neuro-070918-050405","volume":"42","author":"L Nguyen","year":"2019","unstructured":"Nguyen, L., Cleary, J. D. & Ranum, L. P. W. Repeat-associated Non-ATG translation: molecular mechanisms and contribution to neurological disease. Annu. Rev. Neurosci. 42, 227\u2013247 (2019).","journal-title":"Annu. Rev. Neurosci."},{"key":"8578_CR68","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/s41593-020-0590-1","volume":"23","author":"CM Rodriguez","year":"2020","unstructured":"Rodriguez, C. M. et al. A native function for RAN translation and CGG repeats in regulating fragile X protein synthesis. Nat. Neurosci. 23, 386\u2013397 (2020).","journal-title":"Nat. Neurosci."},{"key":"8578_CR69","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1038\/s41593-019-0455-7","volume":"22","author":"SB Yamada","year":"2019","unstructured":"Yamada, S. B. et al. RPS25 is required for efficient RAN translation of C9orf72 and other neurodegenerative disease-associated nucleotide repeats. Nat. Neurosci. 22, 1383\u20131388 (2019).","journal-title":"Nat. Neurosci."},{"key":"8578_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7626","volume":"6","author":"Z-W Du","year":"2015","unstructured":"Du, Z.-W. et al. Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells. Nat. Commun. 6, 6626 (2015).","journal-title":"Nat. Commun."},{"key":"8578_CR71","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1261\/rna.2201210","volume":"16","author":"EB Kramer","year":"2010","unstructured":"Kramer, E. B., Vallabhaneni, H., Mayer, L. M. & Farabaugh, P. J. A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae. RNA 16, 1797\u20131808 (2010).","journal-title":"RNA"},{"key":"8578_CR72","doi-asserted-by":"publisher","first-page":"13353","DOI":"10.1093\/nar\/gku1077","volume":"42","author":"A Arnold","year":"2014","unstructured":"Arnold, A. et al. Functional characterization of C. elegans Y-box-binding proteins reveals tissue-specific functions and a critical role in the formation of polysomes. Nucleic Acids Res. 42, 13353\u201313369 (2014).","journal-title":"Nucleic Acids Res."},{"key":"8578_CR73","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).","journal-title":"Nat. Commun."},{"key":"8578_CR74","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","volume":"51","author":"D Szklarczyk","year":"2023","unstructured":"Szklarczyk, D. et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 51, D638\u2013D646 (2023).","journal-title":"Nucleic Acids Res."},{"key":"8578_CR75","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"8578_CR76","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1093\/bioinformatics\/btq170","volume":"26","author":"MD Wilkerson","year":"2010","unstructured":"Wilkerson, M. D. & Hayes, D. N. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics 26, 1572\u20131573 (2010).","journal-title":"Bioinformatics"},{"key":"8578_CR77","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder, P. & Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinforma. 9, 559 (2008).","journal-title":"BMC Bioinforma."},{"key":"8578_CR78","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v046.i11","volume":"46","author":"P Langfelder","year":"2012","unstructured":"Langfelder, P. & Horvath, S. Fast R functions for robust correlations and hierarchical clustering. J. Stat. Softw. 46, 1\u20137 (2012).","journal-title":"J. Stat. Softw."},{"key":"8578_CR79","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","volume":"14","author":"R Patro","year":"2017","unstructured":"Patro, R., Duggal, G., Love, M. I., Irizarry, R. A. & Kingsford, C. Salmon provides fast and bias-aware quantification of transcript expression. Nat. Methods 14, 417\u2013419 (2017).","journal-title":"Nat. Methods"},{"key":"8578_CR80","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"8578_CR81","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8578_CR82","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"8578_CR83","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"8578_CR84","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923\u2013930 (2014).","journal-title":"Bioinformatics"},{"key":"8578_CR85","doi-asserted-by":"crossref","unstructured":"Wickham, H. Data analysis. In ggplot2: Elegant Graphics for Data Analysis (ed. Wickham, H.) 189\u2013201 (Springer International Publishing, 2016).","DOI":"10.1007\/978-3-319-24277-4_9"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08578-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08578-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08578-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T18:29:18Z","timestamp":1757356158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08578-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,7]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8578"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08578-8","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,7]]},"assertion":[{"value":"15 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1177"}}