Biology subjects

Khorsand, P.

Publications and source records attributed to Khorsand, P..

5 recordsLinked to original sources

bioRxiv2022

Improved structural variant discovery in hard-to-call regions using sample-specific string detection from accurate long reads

Structural variants (SVs) account for a large amount of sequence variability across genomes and play an important role in human genomics and precision medicine. Despite intense efforts over the years, the discovery of SVs in individuals remains challenging due to the diploid and highly repetitive structure of the human genome, and by the presence of SVs that vastly exceed sequencing read lengths. However, the recent introduction of low-error long-read sequencing technologies such as PacBio HiFi may finally enable to overcome these barriers. Here we present SVDSS, a novel hybrid method for discovery of SVs from long-read sequencing technologies (e.g., PacBio HiFi) that combines and effectively leverages mapping-free, mapping-based and assembly-based methodologies for overall superior SV discovery performance. Our experiments on several human samples show that SVDSS outperforms state-of-the-art mapping-based methods for discovery of insertion and deletion SVs in PacBio HiFi reads and achieves significant improvements in calling SVs in repetitive regions of the genome. SVDSS is open source and publicly available at: https://github.com/Parsoa/SVDSS

bioinformatics↗

bioRxiv2021

Comparative genome analysis using sample-specific string detection in accurate long reads

MotivationComparative genome analysis of two or more whole-genome sequenced (WGS) samples is at the core of most applications in genomics. These include discovery of genomic differences segregating in population, case-control analysis in common diseases, and rare disorders. With the current progress of accurate long-read sequencing technologies (e.g., circular consensus sequencing from PacBio sequencers) we can dive into studying repeat regions of genome (e.g., segmental duplications) and hard-to-detect variants (e.g., complex structural variants). ResultsWe propose a novel framework for addressing the comparative genome analysis by discovery of strings that are specific to one genome ("samples-specific" strings). We have developed an accurate and efficient novel method for discovery of samples-specific strings between two groups of WGS samples. The proposed approach will give us the ability to perform comparative genome analysis without the need to map the reads and is not hindered by shortcomings of the reference genome. We show that the proposed approach is capable of accurately finding samples-specific strings representing nearly all variation (> 98%) reported across pairs or trios of WGS samples using accurate long reads (e.g., PacBio HiFi data). AvailabilityThe proposed tool is publicly available at https://github.com/Parsoa/PingPong.

bioinformatics↗

bioRxiv2019

Nebula: Ultra-efficient mapping-free structural variant genotyper

MotivationLarge scale catalogs of common genetic variants (including indels and structural variants) are being created using data from second and third generation whole-genome sequencing technologies. However, the genotyping of these variants in newly sequenced samples is a nontrivial task that requires extensive computational resources. Furthermore, current approaches are mostly limited to only specific types of variants and are generally prone to various errors and ambiguities when genotyping events in repeat regions. Thus we are proposing an ultra-efficient approach for genotyping any type of structural variation that is not limited by the shortcomings and complexities of current mapping-based approaches.\n\nResultsOur method Nebula utilizes the changes in the count of k-mers to predict the genotype of common structural variations. We have shown that not only Nebula is an order of magnitude faster than mapping based approaches for genotyping deletions and mobile-element insertions, but also has comparable accuracy to state-of-the-art approaches. Furthermore, Nebula is a generic framework not limited to any specific type of event.\n\nAvailabilityNebula is publicly available at https://github.com/Parsoa/NebulousSerendipity

bioinformatics↗

bioRxiv2018

Influence of expected reward on perceptual decision making

Perceptual decision making is influenced by reward expected from alternative options or actions, but the underlying neural mechanisms are currently unknown. More specifically, it is debated whether reward effects are mediated through changes in sensory processing and/or later stages of decision making. To address this question, we conducted two experiments in which human subjects made saccades to what they perceived to be the first or second of two visually identical but asynchronously presented targets, while we manipulated expected reward from correct and incorrect responses on each trial. We found that unequal reward caused similar shifts in target selection (reward bias) between the two experiments. Moreover, observed reward biases were independent of the individuals sensitivity to sensory signals. These findings suggest that the observed reward effects were determined heuristically via modulation of decision-making processes instead of sensory processing and thus, are more compatible with response bias rather than perceptual bias. To further explain our findings and uncover plausible neural mechanisms, we simulated our experiments with a cortical network model and tested alternative mechanisms for how reward could exert its influence. We found that our observations are more compatible with reward-dependent input to the output layer of the decision circuit. Together, our results suggest that during a temporal judgment task, the influence of reward information on perceptual choice is more compatible with changing later stages of decision making rather than early sensory processing.

neuroscience↗

bioRxiv2017

Optimal structure of metaplasticity for adaptive learning

Learning from reward feedback in a changing environment requires a high degree of adaptability, yet the precise estimation of reward information demands slow updates. We show that this tradeoff between adaptability and precision, which is present in standard reinforcement-learning models, can be substantially overcome via reward-dependent metaplasticity (reward-dependent synaptic changes that do not always alter synaptic efficacy). Metaplastic synapses achieve both adaptability and precision by forming two separate sets of meta-states: reservoirs and buffers. Synapses in reservoir meta-states do not change their efficacy upon reward feedback, whereas those in buffer meta-states can change their efficacy. Rapid changes in efficacy are limited to synapses occupying buffers, creating a bottleneck that reduces noise without significantly decreasing adaptability. In contrast, more-populated reservoirs can generate a strong signal without manifesting any observable plasticity. We suggest that ubiquitous unreliability of synaptic changes evinces metaplasticity that can provide a robust mechanism for adaptive learning.

neuroscience↗