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Answer ALS is a biological and clinical resource of patient-derived, induced pluripotent stem (iPS) cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This resource provides population-level biological and clinical data that may be employed to identify clinical-molecular-biochemical subtypes of amyotrophic lateral sclerosis (ALS). A unique smartphone-based system was employed to collect deep clinical data, including fine motor activity, speech, breathing and linguistics/cognition. The iPS spinal neurons were blood derived from each patient and these cells underwent multi-omic analytics including whole-genome sequencing, RNA transcriptomics, ATAC-sequencing and proteomics. The intent of these data is for the generation of integrated clinical and biological signatures using bioinformatics, statistics and computational biology to establish patterns that may lead to a better understanding of the underlying mechanisms of disease, including subgroup identification. A web portal for open-source sharing of all data was developed for widespread community-based data analytics.
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http://dx.doi.org/10.1038/s41593-021-01006-0 | DOI Listing |
Neuron
August 2025
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA; Center for the Neural Basis of Cognition, Pittsburgh, PA 15213, USA. Electronic address:
To generate movements, the brain must combine information about movement goal and body posture. The motor cortex (primary motor cortex [M1]) is a key node for the convergence of these information streams. How are posture and goal signals organized within M1's activity to permit the flexible generation of movement commands? To answer this question, we recorded M1 activity while monkeys performed a variety of tasks with the forearm in a range of postures.
View Article and Find Full Text PDFMuscle Nerve
August 2025
Division of Palliative Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Introduction/aims: Specialty palliative care (SPC) aims to optimize quality of life for people with life-limiting illnesses. Previous studies support benefits of SPC for people with amyotrophic lateral sclerosis (pALS) and their caregivers; however, few studies have compared patient and caregiver experiences with ALS care and SPC.
Methods: An online survey assessing satisfaction with care was distributed to pALS and caregivers who had received SPC.
Sci Rep
August 2025
Department of Neurosciences, Cleveland Clinic Research , Cleveland Clinic, Cleveland, OH, 44195, USA.
Amyotrophic lateral sclerosis (ALS) is characterized by a progressive loss of motor function due to degeneration of motor neurons. In addition to motor-related symptoms, increasing evidence from clinical studies indicate lower urinary tract (LUT) dysfunctions (urge incontinence) are found in patients with ALS, which causes a significant negative impact on quality of life. However, it remains unclear whether LUT dysfunction can be validated in preclinical ALS models.
View Article and Find Full Text PDFJ Mol Biol
August 2025
Department of Integrated Structural and Computational Biology, Scripps Research & Howard Hughes Medical Institute, La Jolla, CA, USA. Electronic address:
Predicting multiple conformational states of proteins represents a significant open challenge in structural biology. Increasingly many methods have been reported for perturbing and sampling AlphaFold2 (AF2) (Jumper et al., 2021) to achieve multiple conformational states.
View Article and Find Full Text PDFCommun Biol
August 2025
Department of Anesthesiology, Shanghai Key Laboratory of Perioperative Stress and Protection, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development o
Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The molecular understanding of ALS is hampered by the lack of experimental models recapitulating disease heterogeneity and analytical framework integrating multi-omics datasets. Here, we developed a pipeline integrating machine learning and consensus clustering to analyze a large-scale dataset of patient-derived motor neuron models from Answer ALS.
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