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Novel treatments for autism spectrum disorder based on genomics and systems biology

2021· review· en· W3176976840 on OpenAlexaff
Danielle Baribeau, Evdokia Anagnostou

Bibliographic record

VenuePharmacology & Therapeutics · 2021
Typereview
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsHolland Bloorview Kids Rehabilitation HospitalUniversity of Toronto
Fundersnot available
KeywordsAutism spectrum disorderAutismGenomicsClinical trialNeuroscienceSystems biologyBiomarkerNeurodevelopmental disorderMedicineComputational biologyBiologyBioinformaticsPsychiatryGeneticsGenomeGene

Abstract

fetched live from OpenAlex

BACKGROUND: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with a complex underlying genetic architecture. There are currently no known pharmacologic treatments for the core ASD symptoms of social deficits and restricted/ repetitive behavior. However, there are dozens of clinical trials currently underway that are testing the impact of novel and existing agents on core and associated symptoms in ASD. METHODS: We present a narrative synthesis of the historical and contemporary challenges to drug discovery in ASD. We then provide an overview of novel treatments currently under investigation from a genomics and systems biology perspective. RESULTS: Data driven network and cluster analyses suggest alterations in transcriptional regulation, chromatin remodelling, synaptic transmission, neuropeptide signalling, and/or immunological mechanisms may contribute to or underlie the development of ASD. Agents and upcoming trials targeting each of the above listed systems are reviewed. CONCLUSION: Identifying effective pharmacologic treatments for the core and associated symptom domains in ASD will require further collaboration and innovation in the areas of outcome measurement, biomarker research, and genomics, as well as systematic efforts to identify and treat subgroups of individuals with ASD who may be differentially responsive to specific treatments.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0040.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.172
GPT teacher head0.438
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations50
Published2021
Admission routes1
Has abstractyes

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