Since its inception, deep learning has revolutionized the field of machine learning and data-driven science. One such data-driven science to be transformed by deep learning is genomics. In the past ...decade, numerous genomics studies have adopted deep learning and its applications range from predicting regulatory elements to cancer classification. Despite its dominating efficacy in these applications, deep learning is not without drawbacks. A prominent shortcoming of deep learning is the lack of interpretability. Hence, the main objective of this study is to address this obstacle in the deep learning cancer classification. Here we adopt a feature importance scoring methodology (Gradient-based class activation mapping or Grad-CAM) on a quasi-recurrent neural network model that classify cancer based on FASTA sequencing data. In this study, we managed to formulate a nucleotide-to-genomic-region Grad-CAM scoring methodology, as well as, validate the use this methodology for the chosen model. Consequently, this allows for the utilization of the Grad-CAM scoring methodology for feature importance in deep learning cancer classification. The results from our study identify potential novel candidate genes, genomic elements, and mechanisms for future cancer research.
Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small ...subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).
Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples.
Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate.
Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.
Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 ...surgically resected tumours and the matched adjacent normal tissues to understand the aberrant epigenetic events associated with HCC.
We identified tumour differential enhancers and the associated genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) and Hi-C/HiChIP data from the resected tumour samples of 30 patients with early-stage HCC. This epigenome dataset was analysed with previously reported genome and transcriptome data of the overlapping group of patients from the same cohort. We performed patient-specific differential expression testing using multiregion sequencing data to identify genes that undergo both enhancer and gene expression changes. Based on the genes selected, we identified two patient groups and performed a recurrence-free survival analysis.
We observed large-scale changes in the enhancer distribution between HCC tumours and the adjacent normal samples. Many of the gain-in-tumour enhancers showed corresponding upregulation of the associated genes and vice versa, but much of the enhancer and gene expression changes were patient-specific. A subset of the upregulated genes was activated in a subgroup of patients’ tumours. Recurrence-free survival analysis revealed that the patients with a more robust upregulation of those genes showed a worse prognosis.
We report the genomic enhancer signature associated with differential prognosis in HCC. Findings that cohere with oncofoetal reprogramming in HCC were underpinned by genome-wide enhancer rewiring. Our results present the epigenetic changes in HCC that offer the rational selection of epigenetic-driven gene targets for therapeutic intervention or disease prognostication in HCC.
Lifestyle and environmental-related exposures are the important risk factors of hepatocellular carcinoma (HCC), suggesting that tumour-associated epigenetic dysregulations may significantly underpin HCC. We profiled tumour tissues and their matched normal from 30 patients with early-stage HCC to study the dysregulated epigenetic changes associated with HCC. By also analysing the patients’ RNA-seq and clinical data, we found the signature genes – with epigenetic and transcriptomic dysregulation – associated with worse prognosis. Our findings suggest that systemic approaches are needed to consider the surrounding cellular environmental and epigenetic changes in HCC tumours.
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•Epigenetic dysregulation is prevalent in HCC, accompanied by de novo enhancers.•Differential enhancers and the associated gene expression changes are heterogeneous.•Differential enhancer genes included cellular proliferation and foetal liver markers.•Patients with tumour-activated gain-in-tumour enhancer genes showed worse prognosis.
The cholinergic system of the basal forebrain plays an integral part in behaviors ranging from attention to learning, partly by altering the impact of noise in neural populations. The circuit ...computations underlying cholinergic actions are confounded by recent findings that forebrain cholinergic neurons corelease both acetylcholine (ACh) and GABA. We have identified that corelease of ACh and GABA by cholinergic inputs to the claustrum, a structure implicated in the control of attention, has opposing effects on the electrical activity of claustrum neurons that project to cortical vs. subcortical targets. These actions differentially alter neuronal gain and dynamic range in the two types of neurons. In model networks, the differential effects of ACh and GABA toggle network efficiency and the impact of noise on population dynamics between two different projection subcircuits. Such cholinergic switching between subcircuits provides a potential logic for neurotransmitter corelease in implementing behaviorally relevant computations.
In this paper, a system for the wide area surveillance of general urban environments using multiple Mini-VTOL UAVs is developed. Given the information of terrain and buildings in the target area, the ...problem of (robust) complete coverage of the urban environment is solved by a three-step approximation approach. Firstly, the target area and the observation area are discretized into two sets respectively. Secondly, the visibility between these two sets is checked. Finally, a set covering problem is solved based on the greedy approaches. Two case studies based on real-world data are carried out to demonstrate the effectiveness of our developed system.
Abstract
Topological superconductors (TSC) can host exotic quasiparticles such as Majorana fermions, poised as the fundamental qubits for quantum computers. TSC’s are predicted to form a ...superconducting gap in the bulk, and gapless surface/edges states which can lead to the emergence of Majorana zero energy modes. A candidate TSC is the layered dichalcogenide MoTe
2
, a type-II Weyl (semi)metal in the non-centrosymmetric orthorhombic (T
d
) phase. It becomes superconducting upon cooling below 0.25 K, while under pressure, superconductivity extends well beyond the structural boundary between the orthorhombic and monoclinic (1T′) phases. Here, we show that under pressure, coupled with the electronic band transition across the T
d
to 1T′ phase boundary, evidence for a new phase, we call T
d
* is observed and appears as the volume fraction of the T
d
phase decreases in the coexistence region. T
d
* is most likely centrosymmetric. In the region of space where T
d
* appears, Weyl nodes are destroyed. T
d
* disappears upon entering the monoclinic phase as a function of temperature or on approaching the suppression of the orthorhombic phase under pressure above 1 GPa. Our calculations in the orthorhombic phase under pressure show significant band tilting around the Weyl nodes that most likely changes the spin-orbital texture of the electron and hole pockets near the Fermi surface under pressure that may be linked to the observed suppression of magnetoresistance with pressure.
3D solid robot animation design based on ADAMS Yang, Baojian; Deng, Yongning; Yue, Xia ...
International journal of system assurance engineering and management,
04/2023, Letnik:
14, Številka:
2
Journal Article
Recenzirano
The rapid development of science and technology promotes the intensive development of robotics and the application of ADAMS in the field of robotics is constantly expanding. Research on robot ...kinematics and dynamics is the core issue of biped robot animation simulation. It is of great significance to propose an efficient and improved inverse kinematics algorithm for the development of robotic bionics in China. In this paper, the BIOLOID robot assembly kit is used as the research platform. Based on this, the biped robot kinematics equations and dynamic equations are deduced, and a three-step programming method is used to carry out reasonable gait planning for the biped robot. A simplified virtual prototype model of the lower limb of a biped robot, and the motion trajectories of the joints are input to perform motion simulation of the robot’s static walking. The feasibility of gait planning is verified by analyzing the dynamic images obtained from the simulation experiments and the experimental data of each joint vector. This paper uses the Denavit-Hartenberg rule to construct a biped robot animation simulation kinematics model, deduces a matrix expression describing joint vectors between adjacent links, and solves the biped robot’s positive kinematics equation by chain multiplication rule; An efficient and improved inverse kinematics algorithm is proposed. This solution has the characteristics of high accuracy, high efficiency and few redundant solutions. The experimental study found that the three-step planning method for biped robotic static walking planning is feasible and can reach 98%, and can meet the pre-planning requirements.
Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of ...high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates.
Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone.
A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability.
Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals.
The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models.
ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619.
DERR1-10.2196/54352.
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