Biology subjects

Duarte, E.

Publications and source records attributed to Duarte, E..

6 recordsLinked to original sources

bioRxiv2025

The complete genome of a songbird

Bird genomes are the smallest among amniotes, but remain challenging to assemble due to their structural complexity. This study presents the first fully phased, diploid, telomere-to-telomere (T2T) reference genome for the zebra finch (Taeniopygia guttata), a model organism for neuroscience and evolutionary genomics. Combining multiple sequencing strategies resulted in closing nearly all gaps, adding [~]90 Mbp of previously missing sequence (7.8%). This includes T2T assemblies for all microchromosomes, including dot chromosomes, and the previously almost entirely missing chr16. The T2T genome is comprehensively annotated for genes, repeats, structural variants, and long-read methylation calls. Complete centromeric structures were assembled and annotated along with kinetochore binding sites. Relative to the previous high-quality reference of the Vertebrate Genomes Project, 2,778 (8.51%) previously unassembled or unannotated genes were identified, of which 9% overlap with segmental duplications. This first complete genome of a songbird, now the new public reference, illuminates avian genome architecture and function.

genomics↗

bioRxiv2025

Evaluation of sequencing reads at scale using rdeval

MotivationLarge sequencing data sets are produced and deposited into public archives at unprecedented rates. The availability of tools that can reliably and efficiently generate and store sequencing read summary statistics has become critical. ResultsAs part of the effort by the Vertebrate Genomes Project (VGP) to generate high-quality reference genomes at scale, we sought to address the community need for efficient sequencing data evaluation by developing rdeval, a standalone tool to quickly compute and dynamically display sequencing read metrics. Rdeval can either run on the fly or store key sequence data metrics in read sketches, with dramatic compression gains. Statistics can then be efficiently recalled from sketches for additional processing. Rdeval can convert fa*[.gz] files to and from other popular formats including BAM and CRAM for better compression. Overall, while CRAM achieves the best compression, the gain is marginal, and BAM achieves the best compromise between data compression and accessing speed. Rdeval also generates a detailed visual report with multiple data analytics that can be exported in various formats. We showcase rdevals functionalities using human and VGP read data from different sequencing platforms and species. For PacBio long-read sequencing, our analysis shows dramatic improvements both in read length and quality over time, and a benefit of additional coverage for genome assembly. Availability and implementationRdeval is implemented in C++ for data processivity and in R for data visualization. Precompiled releases (Linux, MacOS, Windows) and commented source code for rdeval are available under MIT license at https://github.com/vgl-hub/rdeval. Documentation is available using ReadTheDocs (https://rdeval-documentation.readthedocs.io). Rdeval is also available in Bioconda and in Galaxy (https://usegalaxy.org). An automated test workflow ensures the consistency of software updates. Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2022

New algorithms for accurate and efficient de-novo genome assembly from long DNA sequencing reads

Producing de-novo genome assemblies for complex genomes is possible thanks to long-read DNA sequencing technologies. However, maximizing the quality of assemblies based on long reads is a challenging task that requires the development of specialized data analysis techniques. In this paper, we present new algorithms for assembling long-DNA sequencing reads from haploid and diploid organisms. The assembly algorithm builds an undirected graph with two vertices for each read based on minimizers selected by a hash function derived from the k-mers distribution. Statistics collected during the graph construction are used as features to build layout paths by selecting edges, ranked by a likelihood function that is calculated from the inferred distributions of features on a subset of safe edges. For diploid samples, we integrated a reimplementation of the ReFHap algorithm to perform molecular phasing. The phasing procedure is used to remove edges connecting reads assigned to different haplotypes and to obtain a phased assembly by running the layout algorithm on the filtered graph. We ran the implemented algorithms on PacBio HiFi and Nanopore sequencing data taken from bacteria, yeast, Drosophila, rice, maize, and human samples. Our algorithms showed competitive efficiency and contiguity of assemblies, as well as superior accuracy in some cases, as compared to other currently used software. We expect that this new development will be useful for researchers building genome assemblies for different species.

bioinformatics↗

bioRxiv2022

Proteome-wide antigenic profiling in Ugandan cohorts identifies associations between age, exposure intensity, and responses to repeat-containing antigens in Plasmodium falciparum

Protection against Plasmodium falciparum, which is primarily antibody-mediated, requires recurrent exposure to develop. The study of both naturally acquired limited immunity and vaccine induced protection against malaria remains critical for ongoing eradication efforts. Towards this goal, we deployed a customized P. falciparum PhIP-seq T7 phage display library containing 238,068 tiled 62-amino acid peptides, covering all known coding regions, including antigenic variants, to systematically profile antibody targets in 198 Ugandan children and adults from high and moderate transmission settings. Repeat elements - short amino acid sequences repeated within a protein - were significantly enriched in antibody targets. While breadth of responses to repeat-containing peptides was twofold higher in children living in the high versus moderate exposure setting, no such differences were observed for peptides without repeats, suggesting that antibody responses to repeat-containing regions may be more exposure dependent and/or less durable in children than responses to regions without repeats. Additionally, short motifs associated with seroreactivity were extensively shared among hundreds of antigens, potentially representing cross- reactive epitopes. PfEMP1 shared motifs with the greatest number of other antigens, partly driven by the diversity of PfEMP1 sequences. These data suggest that the large number of repeat elements and potential cross-reactive epitopes found within antigenic regions of P. falciparum could contribute to the inefficient nature of malaria immunity.

immunology↗

bioRxiv2022

NGSEP 4: Efficient and Accurate Identification of Orthogroups and Whole Genome Alignment

Whole-genome alignment allows researchers to understand the genomic structure and variations among the genomes. Approaches based on direct pairwise comparisons of DNA sequences require large computational capacities. As a consequence, pipelines combining tools for orthologous gene identification and synteny have been developed. In this manuscript, we present the latest functionalities implemented in NGSEP 4, to identify orthogroups and perform whole genome alignments. NGSEP implements functionalities for identification of clusters of homologus genes, synteny analysis and whole genome alignment, and visualization. Our results showed that the NGSEP algorithm for ortholog identification has competitive accuracy and better efficiency in comparison to commonly used tools. The implementation also includes a visualization of the whole genome alignment based on synteny of the orthogroups that were identified, and a reconstruction of the pangenome based on frequencies of the orthogroups among the genomes. Finally, our software includes a new graphical user interface. We expect that these new developments will be very useful for several studies in evolutionary biology and population genomics.

bioinformatics↗

bioRxiv2018

Revealing an extended critical window of recovery post-stroke

The impact of rehabilitation on post-stroke motor recovery and its dependency on the patients chronicity remain unclear. The existence and regularity of a, so called, proportional recovery rule across a range of functional deficits and therapies supports the notion that functional interventions have little or no impact beyond spontaneous recovery rates in a critical window of recovery which lasts from 3 to 6 months post-stroke. In this meta-analysis, we apply a bootstrap analysis method to assess the overall impact of a specific VR-based rehabilitation protocol for the upper extremities on a homogeneous sample of 219 individuals with hemiparesis at various stages post stroke. Our analysis uncovers a precise gradient of sensitivity to treatment that expands more than one year beyond the limits of the so-called critical window of recovery. These findings redefine the limits of the so-called critical window of recovery and suggest that stroke-derived plasticity mechanisms do facilitate functional recovery even at the chronic and late chronic stage.

neuroscience↗