Large-scale annotated dataset for cochlear hair cell detection and classification
(2024) Scientific Data, 11 (1), art. no. 416, .
Buswinka, C.J.a b c , Rosenberg, D.B.a b d , Simikyan, R.G.a , Osgood, R.T.a b e , Fernandez, K.f , Nitta, H.a , Hayashi, Y.a b , Liberman, L.W.a b , Nguyen, E.a , Yildiz, E.g , Kim, J.h i j , Jarysta, A.k , Renauld, J.l , Wesson, E.a , Wang, H.a b , Thapa, P.m , Bordiga, P.a b , McMurtry, N.n , Llamas, J.o p , Kitcher, S.R.e , López-Porras, A.I.q , Cui, R.r , Behnammanesh, G.s , Bird, J.E.s , Ballesteros, A.r , Vélez-Ortega, A.C.q , Edge, A.S.B.a b , Deans, M.R.t u , Gnedeva, K.o p , Shrestha, B.R.a b , Manor, U.d v , Zhao, B.n , Ricci, A.J.i w , Tarchini, B.k x y , Basch, M.L.l , Stepanyan, R.l z , Landegger, L.D.g j , Rutherford, M.A.aa , Liberman, M.C.a b c , Walters, B.J.m , Kros, C.J.e , Richardson, G.P.e , Cunningham, L.L.f , Indzhykulian, A.A.
a Eaton Peabody Laboratories, Mass Eye and Ear, Boston, MA 02114, United States
b Department of Otolaryngology, Head and Neck Surgery, Harvard Medical School, Boston, MA 02114, United States
c Speech and Hearing Biosciences and Technology graduate program, Harvard University, Cambridge, MA 02138, United States
d Department of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, United States
e Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton, United Kingdom
f Section on Sensory Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20814, United States
g Department of Otolaryngology, Head and Neck Surgery, Vienna General Hospital and Medical University of Vienna, Vienna, 1090, Austria
h Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110, United States
i Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
j Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA 94305, United States
k The Jackson Laboratory, Bar Harbor, ME 04609, United States
l Department of Otolaryngology-Head and Neck Surgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States
m The University of Mississippi Medical Center, Department of Otolaryngology – Head and Neck Surgery, Jackson, MS 39216, United States
n Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, United States
o Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, United States
p Tina and Rick Caruso Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, CA 90033, United States
q Department of Physiology, University of Kentucky, Lexington, KY 40536, United States
r Section on Sensory Physiology and Biophysics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20814, United States
s Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, United States
t Department of Neurobiology, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, UT 84112, United States
u Department of Otolaryngology – Head & amp; Neck Surgery, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, UT 84132, United States
v Waitt Advanced Biophotonics Center, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, United States
w Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States
x Tufts University School of Medicine, Boston, MA 02111, United States
y Graduate School of Biomedical Science and Engineering (GSBSE), University of Maine, Orono, ME 04469, United States
z Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States
aa Department of Otolaryngology, Washington University, 660 S. Euclid Avenue, Campus Box 8115, St. Louis, MO 63110, United States
Abstract
Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5–15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease. © The Author(s) 2024.
Funding details
Chan Zuckerberg InitiativeCZI
Silicon Valley Community FoundationSVCF
David F. and Margaret T. Grohne Family Foundation
National Institutes of HealthNIHR01DC000188, R01DC020190, ZIA DC-000079, P50DC015857, T32 DC000038, R21DC020312, R01DC017166, R01DC016365, N00014-18-1-2716, R01DC018827
National Cancer InstituteNCIR01DC021075, CA014195
National Institute on Deafness and Other Communication DisordersNIDCDR01DC014712, R01DC021325, DIR DC000096
Document Type: Data Paper
Publication Stage: Final
Source: Scopus
Exome sequencing of 1190 non-syndromic clubfoot cases reveals HOXD12 as a novel disease gene
(2024) Journal of Medical Genetics, art. no. jmg-2024-109846, .
Charng, W.-L.a , Nikolov, M.a , Shrestha, I.a , Seeley, M.A.b , Josyula, N.S.c , Justice, A.E.c , Dobbs, M.B.d , Gurnett, C.A.a
a Department of Neurology, Washington University in Saint Louis, School of Medicine, Saint Louis, MO, United States
b Department of Orthopaedics, Geisinger Medical Center, Danville, PA, United States
c Department of Population Health Sciences, Geisinger, Danville, PA, United States
d Paley Orthopedic & Spine Institute, West Palm Beach, FL, United States
Abstract
Background: Clubfoot, presenting as a rigid inward and downward turning of the foot, is one of the most common congenital musculoskeletal anomalies. The aetiology of clubfoot is poorly understood and variants in known clubfoot disease genes account for only a small portion of the heritability. Methods: Exome sequence data were generated from 1190 non-syndromic clubfoot cases and their family members from multiple ethnicities. Ultra-rare variant burden analysis was performed comparing 857 unrelated clubfoot cases with European ancestry with two independent ethnicity-matched control groups (1043 in-house and 56 885 gnomAD controls). Additional variants in prioritised genes were identified in a larger cohort, including probands with non-European ancestry. Segregation analysis was performed in multiplex families when available. Results: Rare variants in 29 genes were enriched in clubfoot cases, including PITX1 (a known clubfoot disease gene), HOXD12, COL12A1, COL9A3 and LMX1B. In addition, rare variants in posterior HOX genes (HOX9-13) were enriched overall in clubfoot cases. In total, variants in these genes were present in 8.4% (100/1190) of clubfoot cases with both European and non-European ancestry. Among these, 3 are de novo and 22 show variable penetrance, including 4 HOXD12 variants that segregate with clubfoot. Conclusion: We report HOXD12 as a novel clubfoot disease gene and demonstrate a phenotypic expansion of known disease genes (myopathy gene COL12A1, Ehlers-Danlos syndrome gene COL9A3 and nail-patella syndrome gene LMX1B) to include isolated clubfoot. © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Author Keywords
exome sequencing; genetic diseases, inborn; genetic research; orthopedics; sequence analysis, DNA
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer’s disease late in the disease course and dependent on Lewy pathology burden
(2024) Alzheimer’s and Dementia, .
Levin, J.a b c , Baiardi, S.d , Quadalti, C.e , Rossi, M.e , Mammana, A.e , Vöglein, J.a b , Bernhardt, A.a b , Perrin, R.J.f g , Jucker, M.h i , Preische, O.h i , Hofmann, A.h i , Höglinger, G.U.a b c , Cairns, N.J.j , Franklin, E.E.f g , Chrem, P.k , Cruchaga, C.l , Berman, S.B.m , Chhatwal, J.P.n , Daniels, A.g , Day, G.S.o , Ryan, N.S.p q , Goate, A.M.r , Gordon, B.A.g , Huey, E.D.s , Ibanez, L.l , Karch, C.M.l , Lee, J.-H.t , Llibre-Guerra, J.g , Lopera, F.u , Masters, C.L.v , Morris, J.C.g , Noble, J.M.w , Renton, A.E.x , Roh, J.H.y , Frosch, M.P.z , Keene, C.D.aa , McLean, C.ab , Sanchez-Valle, R.ac , Schofield, P.R.ad ae , Supnet-Bell, C.g , Xiong, C.af , Giese, A.ag , Hansson, O.ah ai , Bateman, R.J.g , McDade, E.g , Parchi, P.d e
a Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
b German Center for Neurodegenerative Diseases, Munich, Germany
c Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
d Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
e IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
f Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, United States
g Department of Neurology, Washington University School of Medicine, Saint Louis, MO, United States
h German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
i Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
j Living Systems Institute, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom
k FLENI, Montañeses 2325 (C1428AQK), Buenos Aires, Argentina
l Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States
m University of Pittsburgh Neurology, Pittsburgh, PA, United States
n Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
o Department of Neurology, Mayo Clinic in Florida, Jacksonville, FL, United States
p Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, United Kingdom
q UK Dementia Research Institute at UCL, London, United Kingdom
r Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
s Butler Hospital, Brown Center for Alzheimer’s Disease Research, Alpert Medical School of Brown University, Providence, RI, United States
t Department of Neurology, Asan Medical Center, Seoul, South Korea
u Grupo de Neurosciencias de Antioquia, Sede de Investigación Universitaria SIU, Medellín, Colombia
v Florey Institute and The University of Melbourne, Melbourne, VIC, Australia
w Department of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and GH Sergievsky Center, Columbia University, New York, NY, United States
x Department of Genetics and Genomic Sciences and Nash Family Dept of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
y Departments of Neurology and Physiology, Korea University College of Medicine, Seoul, South Korea
z MassGeneral Institute for Neurodegenerative Diseases, Neuropathology Service, Massachusetts General Hospital, Boston, MA, United States
aa Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States
ab Department of Anatomical Pathology, AlfredHealth, Melbourne, VIC, Australia
ac Alzheimer’s Disease and Other Cognitive Disorders Unit, Service of Neurology, Hospital Clinic de Barcelona, FRCB-IDIBAPS, Barcelona, Spain
ad Neuroscience Research Australia, Sydney, NSW, Australia
ae School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
af Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, United States
ag Modag GmbH, Wendelsheim, Germany
ah Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden
ai Memory Clinic, Skåne University Hospital, Lund, Sweden
Abstract
INTRODUCTION: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer’s disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo. DISCUSSION: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity. Highlights: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer’s disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP. © 2024 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.
Author Keywords
alpha-synuclein seed amplification assay; Dominantly Inherited Alzheimer Network; Lewy body pathology; real-time quaking-induced conversion
Funding details
Alzheimer’s AssociationAA
Deutsches Zentrum für Neurodegenerative ErkrankungenDZNE
Instituto de Salud Carlos IIIISCIII
Fleni
Fonds de Recherche du Québec – SantéFRQS
Fondation Brain Canada
Japan Agency for Medical Research and DevelopmentAMED
Ministero dell’Istruzione, dell’Università e della RicercaMIUR
Canadian Institutes of Health ResearchCIHR
National Institute on AgingNIA
Ministry of HealthMOH
National Institutes of HealthNIHP30 AG066444, P01AG003991, P01AG026276
Korea Dementia Research CenterKDRCHU21C0066
U19AG032438, PE0000006
Bundesministerium für Bildung und ForschungBMBFFKZ161L0214C CLINSPECT‐M, FKZ161L0214B
Deutsche ForschungsgemeinschaftDFG390857198
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Apparent Diffusion Coefficient of the Optic Nerve Head in Idiopathic Intracranial Hypertension
(2024) Neuro-Ophthalmology, .
Lama, C.a , Derakhshan, J.a b , Wilson, B.c , Snyder, D.c , Tang, Y.a , Van Stavern, G.c
a Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
b Department of Radiology, Abington Hospital, Jefferson Health, Abington, PA, United States
c Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
Abstract
Idiopathic Intracranial Hypertension (IIH) is a condition in which patients have elevated intracranial pressure which does not have an apparent cause. To diagnose IIH, evaluation excluding other causes of elevated pressure must be performed. This typically includes magnetic resonance imaging (MRI) of the brain and venous sinuses. Despite there being known radiographic signs suggestive of IIH on MRI, there currently are no established correlations between radiographic findings and visual outcomes. Previous work revealed diffusion weighted imaging (DWI), a qualitative measurement on MRI, correlated with clinical findings (i.e presence and grade of papilloedema), but not visual outcomes. We hypothesized that the apparent diffusion coefficient (ADC), a quantitative value obtained during clinical MRI, may correlate with visual outcomes. We conducted a retrospective chart review to correlate findings on the ADC sequence on routine brain MRIs in patients with papilloedema with visual outcomes. In 49 patients with IIH, this study shows the ADC in the retrobulbar optic nerve to be 1,487 ± 559 × 10−6 mm2 /s, 15% lower than reported value of 1744 ± 413 in healthy controls. This suggests that there is true restricted diffusion in patients with IIH and papilloedema, as previously reported visually by MRI. However, there was no significant correlation with clinical outcomes of papilloedema grade, mean deviation on standard perimetry, and retinal nerve fibre layer (RNFL) on optical coherence tomography (OCT). We discuss reasons why the ADC measurement may be confounded by motion and partial volume and propose methods that may reduce these confounders for future studies. © 2024 Taylor & Francis Group, LLC.
Author Keywords
apparent diffusion coefficient; diffusion weighted imaging; Idiopathic intracranial hypertension; Papilledema; pseudotumor cerebri
Funding details
Research to Prevent BlindnessRPB
Document Type: Article
Publication Stage: Article in Press
Source: Scopus