Abstract:
:Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with no effective treatments. Numerous RNA-binding proteins (RBPs) have been shown to be altered in ALS, with mutations in 11 RBPs causing familial forms of the disease, and 6 more RBPs showing abnormal expression/distribution in ALS albeit without any known mutations. RBP dysregulation is widely accepted as a contributing factor in ALS pathobiology. There are at least 1542 RBPs in the human genome; therefore, other unidentified RBPs may also be linked to the pathogenesis of ALS. We used IBM Watson® to sieve through all RBPs in the genome and identify new RBPs linked to ALS (ALS-RBPs). IBM Watson extracted features from published literature to create semantic similarities and identify new connections between entities of interest. IBM Watson analyzed all published abstracts of previously known ALS-RBPs, and applied that text-based knowledge to all RBPs in the genome, ranking them by semantic similarity to the known set. We then validated the Watson top-ten-ranked RBPs at the protein and RNA levels in tissues from ALS and non-neurological disease controls, as well as in patient-derived induced pluripotent stem cells. 5 RBPs previously unlinked to ALS, hnRNPU, Syncrip, RBMS3, Caprin-1 and NUPL2, showed significant alterations in ALS compared to controls. Overall, we successfully used IBM Watson to help identify additional RBPs altered in ALS, highlighting the use of artificial intelligence tools to accelerate scientific discovery in ALS and possibly other complex neurological disorders.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Bakkar N,Kovalik T,Lorenzini I,Spangler S,Lacoste A,Sponaugle K,Ferrante P,Argentinis E,Sattler R,Bowser Rdoi
10.1007/s00401-017-1785-8subject
Has Abstractpub_date
2018-02-01 00:00:00pages
227-247issue
2eissn
0001-6322issn
1432-0533pii
10.1007/s00401-017-1785-8journal_volume
135pub_type
杂志文章abstract::Long-term epidemiological studies indicate that environmental factors play a causative role in high-incidence amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) in the western Pacific. An increased risk for disease is acquired in youth and remains for life. The low concentrations of calcium and magnesi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688211
更新日期:1989-01-01 00:00:00
abstract::Mouse embryos were infected with murine cytomegalovirus (MCMV) by injecting the virus into the cerebral ventricles at the late gestation. After deliveries, offspring were fed by the mothers until 4 weeks. Cystic brain lesions, regarded as porencephaly or paraventricular cysts, were observed in about 20% of the MCMV-in...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00293377
更新日期:1991-01-01 00:00:00
abstract::The cholinergic basal forebrain is divided into four subregions (Ch1-4), and cholinergic neuronal loss in the nucleus basalis of Meynert (Ch4) has been correlated with cognitive impairments in both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). However, the Ch1-2 regions, which provide the major choline...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-005-0004-1
更新日期:2006-02-01 00:00:00
abstract::Both protein kinases and phosphoprotein phosphatases are important components of signal transduction systems in cells. Recent studies in Alzheimer's disease (AD) have shown abnormal protein phosphorylation in the cortex suggesting an alteration in these enzymes. In the present study, an antibody against CD45 was used ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294425
更新日期:1991-01-01 00:00:00
abstract::A 77-year-old man suffered intermittent hemiconvulsions of unknown etiology on the left side for a period of about 5 weeks. At the autopsy, there was marked neuronal loss, severe proliferation of astrocytes and spongiform changes in the right cerebral cortex. The cerebral white matter showed loosening with astroglial ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687782
更新日期:1988-01-01 00:00:00
abstract::Cornelia de Lange syndrome (CDLS) is a rare multisystemic malformative syndrome of uncertain etiology characterized by severe psychomotor and mental retardation. Here we report the neuropathological analysis of a 35-year-old patient who displayed the classical clinical symptomatology of CDLS. A congenital dysgenesis o...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-002-0562-4
更新日期:2002-09-01 00:00:00
abstract::Alpha-synuclein (alphaS) and ubiquitin (Ub) are shared constituents of glial cytoplasmic inclusions (GCIs) and Lewy bodies (LBs), both composed of fibrillary structures. Staining profiles of GCIs were investigated with triple immunofluorescence involving immunostaining for alphaS and Ub, both amplified with catalyzed ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-005-1066-9
更新日期:2005-10-01 00:00:00
abstract::To identify antigenic differences between gliomas and normal brain, we have immunohistochemically studied the expression of lymphocyte adhesion molecules (ICAM-1, ICAM-2, ICAM-3, VCAM-1, E-selectin and CD58), epidermal growth factor receptor (EGFR) and extracellular matrix proteins (collagen IV, fibronectin, laminin, ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050696
更新日期:1997-09-01 00:00:00
abstract::Separation of pilocytic astrocytoma from diffuse astrocytomas frequently poses problems mostly related to small sample size. Precise classification and grading are essential due to different therapeutic strategies prompted by diagnoses of pilocytic astrocytoma WHO grade I, diffuse astrocytomas WHO grade II or anaplast...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-009-0550-z
更新日期:2009-09-01 00:00:00
abstract::Seven patients with the typical clinical picture and muscle biopsy findings of classical Werdnig-Hoffmann disease showed Wallerian degeneration in their biopsied sural nerves. In dorsal root ganglia of one patient there were residual nodules and several chromatolytic neurons. By electron microscopy the changes of chro...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690973
更新日期:1978-05-24 00:00:00
abstract::Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-morte...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-017-1686-x
更新日期:2017-03-01 00:00:00
abstract::A system is presented for the classification of chronic herniations of the cerebellar tonsils in the absence of space-occupying intracranial lesions, based on a survey of the literature and 13 own cases. The Arnold-Chiari malformation in adults typically involves herniation of the cerebellar tonsils instead of herniat...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688677
更新日期:1976-03-30 00:00:00
abstract::Activating beta-catenin mutations with aberrant cytoplasmic and nuclear protein accumulation are hallmarks of adamantinomatous craniopharyngiomas (adaCP). These tumours tend to be associated with unfavourable and occasionally disastrous sequelae, as they invade adjacent brain structures such as the hypothalamus. The p...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-010-0642-9
更新日期:2010-05-01 00:00:00
abstract::Abuse of the club drugs Methamphetamine (Meth) and Ecstasy (MDMA) is an international problem. The seriousness of this problem is the result of what appears to be programmed cell death (PCD) occurring within the brain following their use. This follow up study focused on determining which cell types, neurons and/or gli...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-007-0259-9
更新日期:2007-09-01 00:00:00
abstract::Uniform neuropathological changes are described in eight cases of the progressive encephalopathy syndrome with edema, hypsarrhythmia and optic atrophy (PEHO syndrome). Two of the autopsied patients were sisters and two other cases were familial. Macroscopically, cerebral and pronounced cerebellar atrophy was seen, the...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00227717
更新日期:1993-01-01 00:00:00
abstract::Two cases out of a sample of 41 fetuses and infants with prosencephalic malformation, observed at the Institute of Pathology and Department of Neuropathology of the University of Heidelberg, are described here in detail. These cases presented grossly with microcephaly and missing forebrain, appearing to be cases of ap...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/pl00007438
更新日期:2000-03-01 00:00:00
abstract::We recently examined the brain from an 8-month-old infant with Down's syndrome and found argyrophilic plaque-like deposits throughout the neocortex and cerebellum. To ascertain the specificity of this observation, we examined 27 additional brains from the pediatric autopsy service, including 1 from another patient wit...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294258
更新日期:1995-01-01 00:00:00
abstract::Frontotemporal dementia (FTD) is a prevalent neurodegenerative disease of heterogeneous histopathology. Neuropathological subtypes are identified on the basis of the presence or absence of tau- or ubiquitin-positive neuronal inclusions. Our recent work has established four disease stages that are independent of neurop...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-004-0917-0
更新日期:2004-12-01 00:00:00
abstract::Research efforts during the last decade have deciphered the basic molecular mechanisms governing mitochondrial fusion and fission. We now know that in mammalian cells mitochondrial fission is mediated by the large GTPase dynamin-related protein 1 (Drp1) acting in concert with outer mitochondrial membrane (OMM) protein...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-011-0930-z
更新日期:2012-02-01 00:00:00
abstract::The paper describes the clinical and morphological features of a congenital neurological disease affecting two in-bred litter-mate kittens. The principal neurological features were ataxia and dysmetria. In one of the kittens light microscopy revealed widespread vacuolation of white and grey matter of the brain and spi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690561
更新日期:1976-06-15 00:00:00
abstract::We investigated whether the brainstem is affected by the pathologic process of sporadic Creutzfeldt-Jakob disease (sCJD), with particular attention to brainstem atrophy, neuronal loss, pyramidal tract degeneration, and prion protein (PrP) deposition, in 33 patients with sCJD. Brainstem atrophy, particularly in the pon...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-005-0981-0
更新日期:2005-06-01 00:00:00
abstract::A cerebral biopsy was performed in a 39-year-old male patient with subacute paraparesis who later developed severe dementia and moderate cerebellar involvement. The histological examination showed a marked neuronal loss, severe neurofibrillary degeneration, and a great number of senile plaques. No PAS-positive plaques...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00703200
更新日期:1983-01-01 00:00:00
abstract::Neuropathological studies have revealed that the brains of HIV-1-infected AIDS patients show the typical encephalitis and, in addition, neuronal loss. More recently, this neuronal cell loss has been thought to take place via programmed cell death (apoptosis) which has been demonstrated by an in situ end labelling (ISE...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050409
更新日期:1996-01-01 00:00:00
abstract::In adult mice, administration of the anticonvulsive drug phenytoin caused focal swellings along the Purkinje cell axon correlated with ataxia and incoordination of movements. In our model, we used murine cerebellar slice cultures to study the influence of phenytoin on postnatal Purkinje cell axon differentiation. Almo...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050844
更新日期:1998-06-01 00:00:00
abstract::Psammoma bodies in meningocytic whorls were investigated by electron microscopy. In some whorls, connective tissue fibers were seen and membrane-bound vesicles were contiguous to degenerated cells. Some small vesicles, 0.1 to 0.5 micron in diameter, were outlined by plasma membrane (matrix vesicles), other larger ones...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00686081
更新日期:1986-01-01 00:00:00
abstract::Pilocytic astrocytomas (PAs) are the most common brain tumors in pediatric patients and can cause significant morbidity, including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase pathway, but little else is known about their development. To ma...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-013-1124-7
更新日期:2013-08-01 00:00:00
abstract::This report concerns a clinicopathological study of three additional patients with corticobasal degeneration (CBD), described here for the first time, and a clinicopathological correlation between pyramidal signs and upper motor neuron involvement, in ten autopsy cases of CBD, including seven cases reported by us prev...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-004-0966-4
更新日期:2005-04-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are relentlessly progressive neurodegenerative disorders with overlapping clinical, genetic and pathological features. Cytoplasmic inclusions of fused in sarcoma (FUS) are the hallmark of several forms of FTLD and ALS patients with mutati...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-012-1043-z
更新日期:2013-02-01 00:00:00
abstract::Focal cortical dysplasias (FCDs) are increasingly recognized as one of the most common causes of pharmaco-resistant epilepsies. FCDs were recently divided into various clinico-pathological subtypes due to distinct imaging, electrophysiological, and outcome characteristics. In this review, we will overview the internat...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-014-1304-0
更新日期:2014-07-01 00:00:00
abstract::Rats were given isoniazid either in a single large dose or continuously in drinking water and killed 5--105 days later. The distribution of degenerating fibres in various nerves (sensory and mixed) and in various sites along nerves and spinal roots was studied by light and electron microscopy. It was found that sensor...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691784
更新日期:1979-10-01 00:00:00