Biology subjects

Rabiee, M.

Publications and source records attributed to Rabiee, M..

5 recordsLinked to original sources

bioRxiv2026

Length-dependent hypercontractility decoupled from cellular adaptations is the initial phenotype in MYBPC3-haploinsufficient iPSC-derived engineered cardiac tissues

Hypertrophic cardiomyopathy (HCM) is often characterized by a complex landscape of secondary compensatory changes, making it difficult to distinguish primary events triggered by the underlying genetic variants. Here, using patient-derived iPSC-engineered heart tissues cultured in conditions minimizing external stimuli, we identify the initial phenotype of the HCM inducing variant MYBPC3-Q1061X. We demonstrate that initially MYBPC3 haploinsufficiency leads to robust, muscle length-dependent hypercontractility with emerging diastolic dysfunction at higher contraction rates. This phenotype is entirely decoupled from early transcriptional and metabolic stress responses, as evidenced by physiological phenotype and metabolite and cell type-specific transcriptional profiles. Mathematical modeling reveals that the hypercontractile phenotype can be translated to adult cardiac muscle with a small change in myosin availability, amplified by inherent cooperativity within the sarcomere that is instrumental in enhancing the force and the speed of the contraction cycle. Despite the apparent calcium sensitization, these sarcomeric changes do not affect excitation-contraction coupling or calcium buffering in this proximal stage. These results suggest that the primary biophysical defect in MYBPC3-haploinsufficiency manifests as a latent mechanical hypersensitivity that precedes secondary cellular remodeling and functional instability. This initial phenotype provides a window for preventive therapeutic intervention before the onset of permanent cellular remodeling in the heart.

physiology↗

bioRxiv2021

Identification of promising oilseed rape genotypes for the tropical regions of Iran using multivariate analysis

producing new adapted oilseed rape cultivars among the available resources of rapeseed would be a valuable method to increase the cultivar diversity in the tropical regions. Low adaptable and high yield cultivars resources of oilseed rapes are now available in the tropical regions of Iran. The current study aimed to identify new high yield and adaptable genotypes adaptable across various tropical regions. To this end, 20 new genotypes and a check variety (Dalgan) were cultivated in the tropical regions of Iran based on a randomized complete block design (RCBD) with three replications during the 2019 to 2020 cropping season. The experimental sites are composed of five locations, including Gorgan, Sari, Rasht, Borazjan and Zabol. During the growth season, several phenological and quantitative traits were recorded. Combined ANOVA revealed significant genotype by environment interaction for all studied quantitative traits. Days to start flowering and days to end flowering showed the highest heritability. Correlation analysis showed a significant positive relationship between yield and flowering period, the number of sub-branches and also the number of pods per plant, but a negative and significant correlation with the days to maturity. Path analysis showed that the days to maturity had the most negative direct effect on yield and the days to start flowering, while the number of sub-branches had the most positive direct effect on yield. Canonical correlation showed that yield is correlated positively with phenological traits. The principal component analysis showed that the two first components covered 68.07% of all data variations which 12 genotypes were correlated with these two components. Cluster analysis categorized evaluated genotypes into three main groups. Finally, eight genotypes (from class 2 of the cluster) were selected in the current study, which had high yield and adaptability in the tropical regions of Iran.

genetics↗

bioRxiv2019

SODA: Multi-locus species delimitation using quartet frequencies

MotivationSpecies delimitation, the process of deciding how to group a set of organisms into units called species, is one of the most challenging problems in evolutionary computational biology. While many methods exist for species delimitation, most based on the coalescent theory, few are scalable to very large datasets and methods that scale tend to be not accurate. Species delimitation is closely related to species tree inference from discordant gene trees, a problem that has enjoyed rapid advances in recent years. ResultsIn this paper, we build on the accuracy and scalability of recent quartet-based methods for species tree estimation and propose a new method called SODA for species delimitation. SODA relies heavily on a recently developed method for testing zero branch length in species trees. In extensive simulations, we show that SODA can easily scale to very large datasets while maintaining high accuracy. AvailabilityThe code and data presented here are available on https://github.com/maryamrabiee/SODA Contactsmirarab@ucsd.edu

bioinformatics↗

bioRxiv2018

Multi-allele species reconstruction using ASTRAL

Genome-wide phylogeny reconstruction is becoming increasingly common, and one driving factor behind these phylogenomic studies is the promise that the potential discordance between gene trees and the species tree can be modeled. Incomplete lineage sorting is one cause of discordance that bridges population genetic and phylogenetic processes. ASTRAL is a species tree reconstruction method that seeks to find the tree with minimum quartet distance to an input set of inferred gene trees. However, the published ASTRAL algorithm only works with one sample per species. To account for polymorphisms in present-day species, one can sample multiple individuals per species to create multi-allele datasets. Here, we introduce how ASTRAL can handle multi-allele datasets. We show that the quartet-based optimization problem extends naturally, and we introduce heuristic methods for building the search space specifically for the case of multi-individual datasets. We study the accuracy and scalability of the multi-individual version of ASTRAL-III using extensive simulation studies and compare it to NJst, the only other scalable method that can handle these datasets. We do not find strong evidence that using multiple individuals dramatically improves accuracy. When we study the trade-off between sampling more genes versus more individuals, we find that sampling more genes is more effective than sampling more individuals, even under conditions that we study where trees are shallow (median length: {approx} 1Ne) and ILS is extremely high.

bioinformatics↗

bioRxiv2018

INSTRAL: Discordance-aware Phylogenetic Placement using Quartet Scores

Phylogenomic analyses have increasingly adopted species tree reconstruction using methods that account for gene tree discordance using pipelines that require both human effort and computational resources. As the number of available genomes continues to increase, a new problem is facing researchers. Once more species become available, they have to repeat the whole process from the beginning because updating species trees is currently not possible. However, the de novo inference can be prohibitively costly in human effort or machine time. In this paper, we introduce INSTRAL, a method that extends ASTRAL to enable phylogenetic placement. INSTRAL is designed to place a new species on an existing species tree after sequences from the new species have already been added to gene trees; thus, INSTRAL is complementary to existing placement methods that update gene trees.

bioinformatics↗