Biology subjects

Rouse, M.

Publications and source records attributed to Rouse, M..

3 recordsLinked to original sources

bioRxiv2026

From group-level neurophysiological biomarkers to individual-level phenotyping to identify mechanisms of neurodegenerative disease

Precision medicine approaches require physiological effects to be informative when translated to the individual. Reliable group differences may have limited individual value when distributions overlap, mechanisms are heterogeneous, or patients differ in phenotype. A feature can differ between group means and still overlap heavily across individuals Moreover, combinations of physiological abnormalities may reveal subject-level structure that is not captured by any single marker at the group level. We evaluate the translation between group- and individual-level features derived from resting-state magnetoencephalography (MEG) using behavioural-variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy (PSP) as demonstrator conditions. These illnesses have distinct molecular pathology but share the pressing need for therapeutic development and have partially overlapping clinical and physiological features. We combine clinical phenotype, power spectral density (PSD), and latent network mechanisms inferred by dynamic causal modelling (DCM) to compare groups and to access their individuals mapping translations. We used classification as an exploratory probe of how group-defined physiological features from 74 healthy controls, 45 participants with bvFTD and 55 participants with PSP support individual assignment. Clinical scores showed strong individual-level translation, consistent with clinical diagnostic definitions (e.g, controls-vs-PSP accuracy 0.94; bvFTD-vs-PSP accuracy 0.83). MEG spectra feature classified individuals weakly (accuracy ~0.6), despite group level re-organization (e.g., reduced beta-band and increased fronto-insular alpha-phase/beta-amplitude coupling in bvFTD). Inferred biophysical parameters gave intermediate performance (e.g. PSP-vs-control accuracy 0.70; bvFTD-vs-PSP accuracy 0.74) while retaining mechanistic interpretability. Using this approach, experimental medicine studies of neurological disease can formally trade between mechanistic insight and classification performance, in using biomarkers that can account for individual heterogeneity within and between diagnostic groups.

bioengineering↗

bioRxiv2024

Genomes of Aegilops umbellulata provide new insights into unique structural variations and genetic diversity in the U-genome for wheat improvement

Aegilops spp. serve as an important reservoir for novel sources of resistance or tolerance to biotic and abiotic stresses. To harness this reservoir, we have generated a high-quality chromosome-level genome assembly of an Ae. umbellulata accession PI 554389 using a combination of PacBio HiFi, Oxford nanopore, and chromosome conformation capture (Hi-C) sequencing technologies and resequenced 20 Ae. umbellulata genomes using Illumina sequencing. We assembled a 4.20 Gb genome spanned over seven chromosomes, rich in repetitive elements ([~]84%), achieving a QV of 59.54 with 98.14% completeness. The phylogenetic analysis places the U-genome with D-lineage, but major and distinct rearrangements were revealed in the U-genome. Unique transposon landscape of diploid U-genome and complex chromosomal rearrangements, most prominently in 4U and 6U chromosomes uncovered a distinct evolutionary trajectory of Ae. umbellulata. Additionally, the resequencing of geographically and morphologically diverse Ae. umbellulata accessions revealed three distinctive evolutionary sub-populations. Resequencing also identified six new haplotypes for Lr9, the first leaf rust resistance gene introgressed and cloned from Ae. umbellulata. These genomics resources along with high levels of resistance in the resequenced accessions against five devastating wheat diseases affirmed the genetic potential of Ae. umbellulata for wheat improvement.

plant biology↗

bioRxiv2019

Bulked segregant analysis RNA-seq (BSR-Seq) validated a stem resistance locus in Aegilops umbellulata, a wild relative of wheat

Many disease resistance genes that have been transferred from wild relatives to cultivated wheat have played a significant role in wheat production worldwide. Ae. umbellulata is one of the species within the genus Aegilops that have been successfully used as sources of resistance genes to leaf rust, stem rust and powdery mildew. The objectives of the current work was to validate the map position of a major QTL that confers resistance to the stem rust pathogen races Ug99 (TTKSK) and TTTTF with an independent bi-parental mapping population and to refine the QTL region with a bulk segregant analysis approach. Two F2 bi-parental mapping populations were developed from stem rust resistant Ae. umbellulata accessions (PI 298905 and PI 5422375) and stem rust susceptible accessions (PI 542369 and PI 554395). Firstly, one of the two populations was used to map the chromosome location of the resistance gene. Later on, the 2nd population was used to validate the chromosome location in combination with a bulk segregant analysis approach. For the bulk segregant analysis, RNA was extracted from a bulk of leaf tissues of 12 homozygous resistant F3 families, and a separate bulk of 11 susceptible homozygous F3 families derived from the PI 5422375 and PI 554395 cross. The RNA samples of the two bulks and the two parents were sequenced for SNPs identification. Stem rust resistance QTL was validated on chromosome 2U of Ae. umbellulata in the same region in both populations. With bulk segregant analysis, the QTL position was delimited within 3.2 Mbp. Although there were a large number of genes in the orthologous region of the detected QTL on chromosome 2D of Ae. tauschii, we detected only two Ae. umbellulata NLR genes which can be considered as a potential candidate genes.

genomics↗