Gene maps, or annotations, enable us to navigate the functional landscape of our genome. They are a resource upon which virtually all studies depend, from single-gene to genome-wide scales and from ...basic molecular biology to medical genetics. Yet present-day annotations suffer from trade-offs between quality and size, with serious but often unappreciated consequences for downstream studies. This is particularly true for long non-coding RNAs (lncRNAs), which are poorly characterized compared to protein-coding genes. Long-read sequencing technologies promise to improve current annotations, paving the way towards a complete annotation of lncRNAs expressed throughout a human lifetime.
Abstract
The accurate identification and description of the genes in the human and mouse genomes is a fundamental requirement for high quality analysis of data informing both genome biology and ...clinical genomics. Over the last 15 years, the GENCODE consortium has been producing reference quality gene annotations to provide this foundational resource. The GENCODE consortium includes both experimental and computational biology groups who work together to improve and extend the GENCODE gene annotation. Specifically, we generate primary data, create bioinformatics tools and provide analysis to support the work of expert manual gene annotators and automated gene annotation pipelines. In addition, manual and computational annotation workflows use any and all publicly available data and analysis, along with the research literature to identify and characterise gene loci to the highest standard. GENCODE gene annotations are accessible via the Ensembl and UCSC Genome Browsers, the Ensembl FTP site, Ensembl Biomart, Ensembl Perl and REST APIs as well as https://www.gencodegenes.org.
Abstract
Nanopore sequencing enables the efficient and unbiased measurement of transcriptomes. Current methods for transcript identification and quantification rely on mapping reads to a reference ...genome, which precludes the study of species with a partial or missing reference or the identification of disease-specific transcripts not readily identifiable from a reference. We present RATTLE, a tool to perform reference-free reconstruction and quantification of transcripts using only Nanopore reads. Using simulated data and experimental data from isoform spike-ins, human tissues, and cell lines, we show that RATTLE accurately determines transcript sequences and their abundances, and shows good scalability with the number of transcripts.
Information coming from multiple senses, as compared to a single one, typically enhances our performance. The multisensory improvement has been extensively examined in perception studies, as well as ...in tasks involving a motor response like a simple reaction time. However, how this effect extends to more complex behavior, typically involving the coordination of movements, such as bimanual coordination or walking, is still unclear. A critical element in achieving motor coordination in complex behavior is its stability. Reaching a stable state in the coordination pattern allows to sustain complex behavior over time (e.g., without interruption or negative consequences, like falling). This study focuses on the relation between stability in the coordination of movement patterns, like walking, and multisensory improvement. Participants walk with unimodal and audio-tactile metronomes presented either at their preferred rate or at a slower walking rate, the instruction being to synchronize their steps to the metronomes. Walking at a slower rate makes gait more variable than walking at the preferred rate. Interestingly however, the multimodal stimuli enhance the stability of motor coordination but only in the slower condition. Thus, the reduced stability of the coordination pattern (at a slower gait rate) prompts the sensorimotor system to capitalize on multimodal stimulation. These findings provide evidence of a new link between multisensory improvement and behavioral stability, in the context of ecological sensorimotor task.
Many social interactions rely upon mutual information exchange: one member of a pair changes in response to the other while at the same time producing actions that alter the behavior of the other. ...However, little is known about how such social processes are integrated in the brain. Here, we used a specially designed dual-electroencephalogram system and the conceptual framework of coordination dynamics to identify neural signatures of effective, real-time coordination between people and its breakdown or absence. High-resolution spectral analysis of electrical brain activity before and during visually mediated social coordination revealed a marked depression in occipital alpha and rolandic mu rhythms during social interaction that was independent of whether behavior was coordinated or not. In contrast, a pair of oscillatory components (phi₁ and phi₂) located above right centro-parietal cortex distinguished effective from ineffective coordination: increase of phi₁ favored independent behavior and increase of phi₂ favored coordinated behavior. The topography of the phi complex is consistent with neuroanatomical sources within the human mirror neuron system. A plausible mechanism is that the phi complex reflects the influence of the other on a person's ongoing behavior, with phi₁ expressing the inhibition of the human mirror neuron system and phi₂ its enhancement.
Abstract Long-read RNA sequencing is essential to produce accurate and exhaustive annotation of eukaryotic genomes. Despite advancements in throughput and accuracy, achieving reliable end-to-end ...identification of RNA transcripts remains a challenge for long-read sequencing methods. To address this limitation, we develop CapTrap-seq, a cDNA library preparation method, which combines the Cap-trapping strategy with oligo(dT) priming to detect 5’ capped, full-length transcripts. In our study, we evaluate the performance of CapTrap-seq alongside other widely used RNA-seq library preparation protocols in human and mouse tissues, employing both ONT and PacBio sequencing technologies. To explore the quantitative capabilities of CapTrap-seq and its accuracy in reconstructing full-length RNA molecules, we implement a capping strategy for synthetic RNA spike-in sequences that mimics the natural 5’cap formation. Our benchmarks, incorporating the Long-read RNA-seq Genome Annotation Assessment Project (LRGASP) data, demonstrate that CapTrap-seq is a competitive, platform-agnostic RNA library preparation method for generating full-length transcript sequences.
Abstract
We aimed to investigate the amyloid and tau PET imaging signatures of patients with amnestic syndrome of the hippocampal type (ASHT) and study their clinical and imaging progression ...according to their initial PET imaging status. Thirty-six patients with a progressive ASHT and 30 controls underwent a complete neuropsychological assessment, 3 T brain MRI,
11
C-PiB and
18
F-Flortaucipir PET imaging. Subjects were clinically followed-up annually over 2 years, with a second 3 T MRI (
n
= 27 ASHT patients,
n
= 28 controls) and tau-PET (
n
= 20 ASHT patients) at the last visit. At baseline, in accordance with the recent biological definition of Alzheimer’s disease (AD), the AD PET signature was defined as the combination of (i) positive cortical amyloid load, and (ii) increased tau tracer binding in the entorhinal cortices and at least one of the following regions: amygdala, parahippocampal gyri, fusiform gyri. Patients who did not meet these criteria were considered to have a non-AD pathology (SNAP). Twenty-one patients were classified as AD and 15 as SNAP. We found a circumscribed tau tracer retention in the entorhinal cortices and/or amygdala in 5 amyloid-negative SNAP patients. At baseline, the SNAP patients were older and had lower
ApoE
ε4 allele frequency than the AD patients, but both groups did not differ regarding the neuropsychological testing and medial temporal lobe atrophy. During the 2-year follow-up, the episodic memory and language decline, as well as the temporo-parietal atrophy progression, were more pronounced in the AD sub-group, while the SNAP patients had a more pronounced progression of atrophy in the frontal lobes. Longitudinal tau tracer binding increased in AD patients but remained stable in SNAP patients. At baseline, distinct amyloid and tau PET signatures differentiated early AD and SNAP patients despite identical cognitive profiles characterized by an isolated ASHT and a similar degree of medial temporal atrophy. During the longitudinal follow-up, AD and SNAP patients diverged regarding clinical and imaging progression. Among SNAP patients, tau PET imaging could detect a tauopathy restricted to the medial temporal lobes, which was possibly explained by primary age-related tauopathy.
The analysis of biomarkers in biological fluids, also known as liquid biopsies, is seen with great potential to diagnose complex diseases such as cancer with a high sensitivity and minimal ...invasiveness. Although it can target any biomolecule, most liquid biopsy studies have focused on circulating nucleic acids. Historically, studies have aimed at the detection of specific mutations on cell-free DNA (cfDNA), but recently, the study of cell-free RNA (cfRNA) has gained traction. Since 2020, a handful of cfDNA tests have been approved for therapy selection by the FDA, however, no cfRNA tests are approved to date. One of the main drawbacks in the field of RNA-based liquid biopsies is the low reproducibility of the results, often caused by technical and biological variability, a lack of standardized protocols and insufficient cohorts. In this review, we will identify the main challenges and biases introduced during the different stages of biomarker discovery in liquid biopsies with cfRNA and propose solutions to minimize them.
Measuring the morphology of brain sulci has been recently proposed as a novel imaging approach in Alzheimer's disease (AD). We aimed to investigate the relevance of such an approach in AD, by ...exploring its (1) clinical relevance in comparison with traditional imaging methods, (2) relationship with amyloid deposition, (3) association with cognitive functions. Here, 51 patients (n = 32 mild cognitive impairment/mild dementia-AD, n = 19 moderate/severe dementia-AD) diagnosed according to clinical-biological criteria (CSF biomarkers and amyloid-PET) and 29 controls (with negative amyloid-PET) underwent neuropsychological and 3T-MRI examinations. Mean sulcal width (SW) and mean cortical thickness around the sulcus (CT-S) were automatically measured. We found higher SW and lower CT-S in patients with AD than in controls. These differences were more pronounced at later stages of the disease and provided the best diagnostic accuracies among the imaging markers. Correlations were not found between CT-S or SW and amyloid deposition but between specific cognitive functions and regional CT-S/SW in key associated regions. Sulcal morphology is a good supporting diagnosis tool that reflects the main cognitive impairments in AD. It could be considered as a good surrogate marker to evaluate the efficacy of new drugs.
•Examination of sulcal morphology alterations is a good diagnosis tool for Alzheimer's disease.•This imaging marker is more accurate than traditional imaging tools such as hippocampal volume.•Sulcal morphology alterations are correlated to specific cognitive impairment observed.•Sulcal morphology alterations are related to disease severity.
The brain has the remarkable ability to bind together inputs from different sensory origin into a coherent percept. Behavioral benefits can result from such ability, e.g., a person typically responds ...faster and more accurately to cross-modal stimuli than to unimodal stimuli. To date, it is, however, largely unknown whether such multisensory benefits, shown for discrete reactive behaviors, generalize to the continuous coordination of movements. The present study addressed multisensory integration from the perspective of bimanual coordination dynamics, where the perceptual activity no longer triggers a single response but continuously guides the motor action. The task consisted in coordinating anti-symmetrically the continuous flexion–extension of the index fingers, while synchronizing with an external pacer. Three different configurations of metronome were tested, for which we examined whether a cross-modal pacing (audio–tactile beats) improved the stability of the coordination in comparison with unimodal pacing condition (auditory or tactile beats). We found a more stable bimanual coordination for cross-modal pacing, but only when the metronome configuration directly matched the anti-symmetric coordination pattern. We conclude that multisensory integration can benefit the continuous coordination of movements; however, this is constrained by whether the perceptual and motor activities match in space and time.
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