Dataset Information

Predictions through evidence accumulation over time.

ABSTRACT: It has been proposed that the brain specializes in predicting future states of the environment. These predictions are probabilistic, and must be continuously updated on the basis of their mismatch with actual evidence. Although electrophysiological data disclose neural activity patterns in relation to predictive processes, little is known about how this activity supports prediction build-up through evidence accumulation. Here we addressed this gap. Participants were required to make moment-by-moment predictions about stimuli presented in sequences in which gathering evidence from previous items as they were presented was either possible or not. Two event-related potentials (ERP), a frontocentral P2 and a central P3, were sensitive to information accumulation throughout the sequence. Time-frequency (TF) analyses revealed that prediction build-up process also modulated centrally distributed theta activity, and that alpha power was suppressed in anticipation to fully predictable stimuli. Results are in agreement with the notion of predictions as probability distributions and highlight the ability of observers to extract those probabilities in a changing environment and to adjust their predictions consequently.

SUBMITTER: Darriba A

PROVIDER: S-EPMC5765034 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Predictions through evidence accumulation over time.

Darriba Álvaro Á Waszak Florian F

Scientific reports 20180111 1

It has been proposed that the brain specializes in predicting future states of the environment. These predictions are probabilistic, and must be continuously updated on the basis of their mismatch with actual evidence. Although electrophysiological data disclose neural activity patterns in relation to predictive processes, little is known about how this activity supports prediction build-up through evidence accumulation. Here we addressed this gap. Participants were required to make moment-by-mo ...[more]

PMID: 29323172

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Project description:Interpreting the clinical consequences of genetic variants is the central problem in modern clinical genomics, for both hereditary diseases and oncology. However, clinical validation lags behind the pace of discovery, leading to distressing uncertainty for patients, physicians and researchers. This "interpretation gap" changes over time as evidence accumulates, and variants initially deemed of uncertain (VUS) significance may be subsequently reclassified in pathogenic/benign. We previously developed RENOVO, a random forest-based tool able to predict variant pathogenicity based on publicly available information from GnomAD and dbNFSP, and tested on variants that have changed their classification status over time. Here, we comprehensively evaluated the accuracy of RENOVO predictions on variants that have been reclassified over the last four years. we retrieved 16 retrospective instances of the ClinVar database, every 3 months since March 2020 to March 2024, and analyzed time trends of variant classifications. We identified variants that changed their status over time and compared RENOVO predictions generated in 2020 with the actual reclassifications. VUS have become the most represented class in ClinVar (44.97% vs. 9.75% (likely) pathogenic and 40,33% (likely) benign). The rate of VUS reclassification is linear and slow compared to the rate of VUS reporting, exponential and currently ~ 30x faster, creating a growing divide between what can be sequenced vs. what can be interpreted. Out of 10,196 VUS variants in January 2020 that have undergone a clinically meaningful reclassification to march 2024, RENOVO correctly classified 82.6% in 2020. In addition, RENOVO correctly identified the majority of the few variants that switched clinically meaningful classes (e.g., from benign to pathogenic and vice versa). We highlight variant classes and clinically relevant genes for which RENOVO provides particularly accurate estimates. In particularly, genes characterized by large prevalence of high- or low-impact variants (e.g., POLE, NOTCH1, FANCM etc.). Suboptimal RENOVO predictions mostly concern genes validated through dedicated consortia (e.g., BRCA1/2), in which RENOVO would anyway have a limited impact. Time trend analysis demonstrates that the current model of variant interpretation cannot keep up with variant discovery. Machine learning-based tools like RENOVO confirm high accuracy that can aid in clinical practice and research.

Project description:Since the first case of COVID-19 in December 2019 in Wuhan, China, SARS-CoV-2 has spread worldwide and within a year and a half has caused 3.56 million deaths globally. With dramatically increasing infection numbers, and the arrival of new variants with increased infectivity, tracking the evolution of its genome is crucial for effectively controlling the pandemic and informing vaccine platform development. Our study explores evolution of SARS-CoV-2 in a representative cohort of sequences covering the entire genome in the United States, through all of 2020 and early 2021. Strikingly, we detected many accumulating Single Nucleotide Variations (SNVs) encoding amino acid changes in the SARS-CoV-2 genome, with a pattern indicative of RNA editing enzymes as major mutators of SARS-CoV-2 genomes. We report three major variants through October of 2020. These revealed 14 key mutations that were found in various combinations among 14 distinct predominant signatures. These signatures likely represent evolutionary lineages of SARS-CoV-2 in the U.S. and reveal clues to its evolution such as a mutational burst in the summer of 2020 likely leading to a homegrown new variant, and a trend towards higher mutational load among viral isolates, but with occasional mutation loss. The last quartile of 2020 revealed a concerning accumulation of mostly novel low frequency replacement mutations in the Spike protein, and a hypermutable glutamine residue near the putative furin cleavage site. Finally, end of the year data and 2021 revealed the gradual increase to prevalence of known variants of concern, particularly B.1.1.7, that have acquired additional Spike mutations. Overall, our results suggest that predominant viral genomes are dynamically evolving over time, with periods of mutational bursts and unabated mutation accumulation. This high level of existing variation, even at low frequencies and especially in the Spike-encoding region may become problematic when super-spreader events, akin to serial Founder Events in evolution, drive these rare mutations to prominence.

Dataset Information

Predictions through evidence accumulation over time.

Publications

Predictions through evidence accumulation over time.

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