当前共找到 1194 篇文献分享,本页显示第 501 - 520 篇。
501.
颜林林 (2023-06-24 21:59):
#paper doi:10.1093/nar/gkad526 Nucleic Acids Research, 2023, Precise characterization of somatic complex structural variations from tumor/control paired long-read sequencing data with nanomonsv. 这是一篇生信文章,作者开发了一个工具nanomonsv,基于配对的肿瘤和对照样本的三代测序数据,鉴定构变异(SV)。该程序包括两个模块:Canonical SV module 和 Single breakend SV module,前者采取寻找跨越断点的多条支持reads的策略,后者则先对断点单侧的序列进行合并,再通过soft clip部分去寻找(可能在基因组上缺失或难以判定)的另一侧序列。通过对这两种策略的实现、优化和整合,提高了对SV的鉴定性能。本文在三个肿瘤细胞系样本(及其对应对照样本)的三代数据上,对所开发的工具进行了实测和评估,并使用PCR方法对部分结果进行了验证。此外,本文还对甲基化、重复序列、移动元件、病毒序列整合等序列特性进行了分析,以进一步充实文章的内容。
IF:16.600Q1 Nucleic acids research, 2023-08-11. DOI: 10.1093/nar/gkad526 PMID: 37336583
Abstract:
We present our novel software, nanomonsv, for detecting somatic structural variations (SVs) using tumor and matched control long-read sequencing data with a single-base resolution. The current version of nanomonsv includes … >>>
We present our novel software, nanomonsv, for detecting somatic structural variations (SVs) using tumor and matched control long-read sequencing data with a single-base resolution. The current version of nanomonsv includes two detection modules, Canonical SV module, and Single breakend SV module. Using tumor/control paired long-read sequencing data from three cancer and their matched lymphoblastoid lines, we demonstrate that Canonical SV module can identify somatic SVs that can be captured by short-read technologies with higher precision and recall than existing methods. In addition, we have developed a workflow to classify mobile element insertions while elucidating their in-depth properties, such as 5' truncations, internal inversions, as well as source sites for 3' transductions. Furthermore, Single breakend SV module enables the detection of complex SVs that can only be identified by long-reads, such as SVs involving highly-repetitive centromeric sequences, and LINE1- and virus-mediated rearrangements. In summary, our approaches applied to cancer long-read sequencing data can reveal various features of somatic SVs and will lead to a better understanding of mutational processes and functional consequences of somatic SVs. <<<
翻译
502.
小W (2023-05-31 23:59):
#paper doi:https://doi.org/10.1016/j.cell.2023.03.035 Massively parallel base editing to map variant effects in human hematopoiesis 本文介绍了一种基因编辑工具:碱基编辑器,在原代人类造血干细胞进行研究的文章。通过结合碱基编辑器和单细胞rna 测序技术,进行了以下研究:对人类全基因组关联研究发现的大量单核苷酸变异的实验评估,对患者临床测序鉴定突变的致病性评估。
IF:45.500Q1 Cell, 2023-05-25. DOI: 10.1016/j.cell.2023.03.035 PMID: 37137305
Abstract:
Systematic evaluation of the impact of genetic variants is critical for the study and treatment of human physiology and disease. While specific mutations can be introduced by genome engineering, we … >>>
Systematic evaluation of the impact of genetic variants is critical for the study and treatment of human physiology and disease. While specific mutations can be introduced by genome engineering, we still lack scalable approaches that are applicable to the important setting of primary cells, such as blood and immune cells. Here, we describe the development of massively parallel base-editing screens in human hematopoietic stem and progenitor cells. Such approaches enable functional screens for variant effects across any hematopoietic differentiation state. Moreover, they allow for rich phenotyping through single-cell RNA sequencing readouts and separately for characterization of editing outcomes through pooled single-cell genotyping. We efficiently design improved leukemia immunotherapy approaches, comprehensively identify non-coding variants modulating fetal hemoglobin expression, define mechanisms regulating hematopoietic differentiation, and probe the pathogenicity of uncharacterized disease-associated variants. These strategies will advance effective and high-throughput variant-to-function mapping in human hematopoiesis to identify the causes of diverse diseases. <<<
翻译
503.
Ricardo (2023-05-31 23:53):
#paper DOI:https://doi.org/10.48550/arXiv.2304.00217 DrDisco: Deep Registration for Distortion Correction of Diffusion MRI with single phase-encoding 弥散加权磁共振成像(DW-MRI)是一种对人脑白质束进行无创成像的方法。dw - mri通常采用高梯度回波平面成像(echo-planar imaging, EPI)获得,会引入严重的几何畸变,影响进一步的分析。大多数校正失真的工具需要两张不同相位编码方向获取的最小加权DW-MRI图像(B0),处理每个受试者可能需要数小时。由于大量扩散数据仅在单一相位编码方向下获取,现有方法的应用受到限制。本文提出一种基于深度学习的配准方法,仅使用从单一相位编码方向获得的B0来纠正失真。通过一个深度学习模型,将未失真的t1加权图像与失真的B0图像进行配准,以消除失真。在训练过程中应用可微的互信息损失来改善模态间对齐。在Human Connectome Project数据集上的实验表明,所提出的方法在多个指标上优于SyN和VoxelMorph,且处理一个受试者只需几秒钟。
Abstract:
Diffusion-weighted magnetic resonance imaging (DW-MRI) is a non-invasive way of imaging white matter tracts in the human brain. DW-MRIs are usually acquired using echo-planar imaging (EPI) with high gradient fields, … >>>
Diffusion-weighted magnetic resonance imaging (DW-MRI) is a non-invasive way of imaging white matter tracts in the human brain. DW-MRIs are usually acquired using echo-planar imaging (EPI) with high gradient fields, which could introduce severe geometric distortions that interfere with further analyses. Most tools for correcting distortion require two minimally weighted DW-MRI images (B0) acquired with different phase-encoding directions, and they can take hours to process per subject. Since a great amount of diffusion data are only acquired with a single phase-encoding direction, the application of existing approaches is limited. We propose a deep learning-based registration approach to correct distortion using only the B0 acquired from a single phase-encoding direction. Specifically, we register undistorted T1-weighted images and distorted B0 to remove the distortion through a deep learning model. We apply a differentiable mutual information loss during training to improve inter-modality alignment. Experiments on the Human Connectome Project dataset show the proposed method outperforms SyN and VoxelMorph on several metrics, and only takes a few seconds to process one subject. <<<
翻译
504.
笑对人生 (2023-05-31 23:47):
#paper doi: 10.1038/s41467-023-36948-5. Yang B, et al. CTCF controls three-dimensional enhancer network underlying the inflammatory response of bone marrow-derived dendritic cells. Nat Commun. 2023 Mar 8;14(1):1277.  树突状细胞是一类重要的抗原呈递细胞,参与先天性和适应性免疫的精密调控过程。激活的树突状细胞能够通过上调主要相容性复合物、共刺激分子和多种促炎细胞因子调节淋巴细胞的激活和分化。然而,树突状细胞的异常激活可能会导致多发硬化等自身免疫性疾病。因此,深入研究树突状细胞激活的内在机制对相关疾病治疗策略的制定具有重要意义。本研究结合HiC、ChIP-seq和RNAseq三种组学技术,在三维基因组层面揭示了骨髓来源的树突状细胞激活重要机制。研究结果显示,染色质loop结构和增强子-启动子互作重编程诱导树突状细胞激活;树突状细胞CTCF缺失后会引起粒细胞-巨噬细胞集落刺激因子(GM-CSF)介导的JAK2/STAT5信号通路,最终导致NF-kB复合物失活;CTCF是NK-kB依赖染色质互作和增强与Th1和Th17细胞分化相关的促炎细胞因子表达的关键分子。
IF:14.700Q1 Nature communications, 2023-03-08. DOI: 10.1038/s41467-023-36948-5 PMID: 36882470
Abstract:
Dendritic cells are antigen-presenting cells orchestrating innate and adaptive immunity. The crucial role of transcription factors and histone modifications in the transcriptional regulation of dendritic cells has been extensively studied. … >>>
Dendritic cells are antigen-presenting cells orchestrating innate and adaptive immunity. The crucial role of transcription factors and histone modifications in the transcriptional regulation of dendritic cells has been extensively studied. However, it is not been well understood whether and how three-dimensional chromatin folding controls gene expression in dendritic cells. Here we demonstrate that activation of bone marrow-derived dendritic cells induces extensive reprogramming of chromatin looping as well as enhancer activity, both of which are implicated in the dynamic changes in gene expression. Interestingly, depletion of CTCF attenuates GM-CSF-mediated JAK2/STAT5 signaling, resulting in defective NF-κB activation. Moreover, CTCF is necessary for establishing NF-κB-dependent chromatin interactions and maximal expression of pro-inflammatory cytokines, which prime Th1 and Th17 cell differentiation. Collectively, our study provides mechanistic insights into how three-dimensional enhancer networks control gene expression during bone marrow-derived dendritic cells activation, and offers an integrative view of the complex activities of CTCF in the inflammatory response of bone marrow-derived dendritic cells. <<<
翻译
505.
半面阳光 (2023-05-31 23:32):
#paper DOI: 10.12688/wellcomeopenres.10069.1,Wellcome Open Res, 2016, Accurate clinical detection of exon copy number variants in a targeted NGS panel using DECoN, 一篇方法学文章,作者开发了一个用于准确检出外显子测序数据中的CNVs的工具-DECoN。同时采用近2000个样本对DECoN的性能进行了验证和评估。WES测序在临床诊断的应用逐渐广泛,这篇文章中的工具为充分利用WES数据提供了一种可能。
Abstract:
Targeted next generation sequencing (NGS) panels are increasingly being used in clinical genomics to increase capacity, throughput and affordability of gene testing. Identifying whole exon deletions or duplications (termed exon … >>>
Targeted next generation sequencing (NGS) panels are increasingly being used in clinical genomics to increase capacity, throughput and affordability of gene testing. Identifying whole exon deletions or duplications (termed exon copy number variants, 'exon CNVs') in exon-targeted NGS panels has proved challenging, particularly for single exon CNVs. We developed a tool for the Detection of Exon Copy Number variants (DECoN), which is optimised for analysis of exon-targeted NGS panels in the clinical setting. We evaluated DECoN performance using 96 samples with independently validated exon CNV data. We performed simulations to evaluate DECoN detection performance of single exon CNVs and to evaluate performance using different coverage levels and sample numbers. Finally, we implemented DECoN in a clinical laboratory that tests and with the TruSight Cancer Panel (TSCP). We used DECoN to analyse 1,919 samples, validating exon CNV detections by multiplex ligation-dependent probe amplification (MLPA). In the evaluation set, DECoN achieved 100% sensitivity and 99% specificity for BRCA exon CNVs, including identification of 8 single exon CNVs. DECoN also identified 14/15 exon CNVs in 8 other genes. Simulations of all possible BRCA single exon CNVs gave a mean sensitivity of 98% for deletions and 95% for duplications. DECoN performance remained excellent with different levels of coverage and sample numbers; sensitivity and specificity was >98% with the typical NGS run parameters. In the clinical pipeline, DECoN automatically analyses pools of 48 samples at a time, taking 24 minutes per pool, on average. DECoN detected 24 BRCA exon CNVs, of which 23 were confirmed by MLPA, giving a false discovery rate of 4%. Specificity was 99.7%. DECoN is a fast, accurate, exon CNV detection tool readily implementable in research and clinical NGS pipelines. It has high sensitivity and specificity and acceptable false discovery rate. DECoN is freely available at www.icr.ac.uk/decon. <<<
翻译
506.
小擎子 (2023-05-31 23:05):
#paper 10.1126/science.1257481 Science, 2014 , High thermodynamic stability of parametrically designed helical bundles 参数化设计的螺旋束的高热力学稳定性。通过参数化骨架生成与Rosetta蛋白质设计相结合的方法,生成非常稳定的蛋白质结构。不依赖已知序列基序的情况下轻松生成具有精细几何形状的超稳定蛋白质,有助于基于蛋白质的纳米结构、疗法和催化剂的设计。核心是参数化设计,依靠的是对Crick Coiled-coil方程做参数扰动。0.1埃的扰动可以生成成千上万个α螺旋设计骨架。文章找了几种低能量的设计做测试,实验验证,晶体结构与设计一致,且稳定性超好,堪称“砖头”。ps 因文章较早,用的是Rosetta设计序列,如果改用ProteinMPNN,可以生成有更多活性表达的蛋白质序列。
Abstract:
We describe a procedure for designing proteins with backbones produced by varying the parameters in the Crick coiled coil-generating equations. Combinatorial design calculations identify low-energy sequences for alternative helix supercoil … >>>
We describe a procedure for designing proteins with backbones produced by varying the parameters in the Crick coiled coil-generating equations. Combinatorial design calculations identify low-energy sequences for alternative helix supercoil arrangements, and the helices in the lowest-energy arrangements are connected by loop building. We design an antiparallel monomeric untwisted three-helix bundle with 80-residue helices, an antiparallel monomeric right-handed four-helix bundle, and a pentameric parallel left-handed five-helix bundle. The designed proteins are extremely stable (extrapolated ΔGfold > 60 kilocalories per mole), and their crystal structures are close to those of the design models with nearly identical core packing between the helices. The approach enables the custom design of hyperstable proteins with fine-tuned geometries for a wide range of applications. <<<
翻译
507.
林海onrush (2023-05-31 22:41):
#paper,Mastering the Game of Stratego with Model-Free Multiagent Reinforcement Learning,DOI: 10.1126/science.add4679,强化学习在军事战略模拟领域的尝试如何?作者团队给出了一个可行的思路:如何使用无模型的多智能体强化学习来掌握战略游戏Stratego。本文提出了DeepNash,一个能够学习玩不完美信息游戏Stratego1从零开始,直至达到人类专家的水平。战略游戏是人工智能尚未掌握的少数标志性棋盘游戏之一。(AI)还没有掌握的少数标志性棋盘游戏之一。这个流行的游戏有一个巨大的游戏树10535个节点,也就是说,比围棋大0175倍。它有它还有一个额外的复杂性,就是需要在不完美的信息下进行决策。在tratego中,决策是在大量没有明显的离散行动的情况下做出的。行动和结果之间没有明显的联系。情节很长,在玩家获胜之前往往有几百步棋,而且战略游戏中的情况不容易被分解为可管理的大小的子问题。由于这些原因,几十年来《策略》一直是人工智能领域的一个巨大挑战,而现有的人工智能方法几乎没有达到业余水平。业余水平的游戏。DeepNash使用了一种游戏理论的、无模型的深度强化学习方法,不需要搜索,它通过自我游戏来学习掌握Stratego。正则化纳什动力学(R-aD)算法是DeepNash的一个关键组成部分,它收敛到一个近似的纳什均衡,通过直接修改基础的多Agent学习动态性。DeepNash击败了Stratego中现有的最先进的人工智能方法。并在Gravon游戏平台上取得了年度(2022年)和历史上前三名的成绩。平台上取得了年度(2022年)和历史上的前三名,与人类专家玩家竞争。本文的工作很有意思,有进一步探索的空间。个人认为此思路在MOBA类游戏中有很强的可拓展性。
Abstract:
We introduce DeepNash, an autonomous agent that plays the imperfect information game Stratego at a human expert level. Stratego is one of the few iconic board games that artificial intelligence … >>>
We introduce DeepNash, an autonomous agent that plays the imperfect information game Stratego at a human expert level. Stratego is one of the few iconic board games that artificial intelligence (AI) has not yet mastered. It is a game characterized by a twin challenge: It requires long-term strategic thinking as in chess, but it also requires dealing with imperfect information as in poker. The technique underpinning DeepNash uses a game-theoretic, model-free deep reinforcement learning method, without search, that learns to master Stratego through self-play from scratch. DeepNash beat existing state-of-the-art AI methods in Stratego and achieved a year-to-date (2022) and all-time top-three ranking on the Gravon games platform, competing with human expert players. <<<
翻译
508.
符毓 Yu (2023-05-31 22:40):
#paper doi.org/10.48550/arXiv.2212.12669 Nature, 2023, On Realization of Intelligent Decision-Making in the Real World: A Foundation Decision Model Perspective。本文讨论了由于不确定性和动态环境,在现实场景中实现机器主导的智能决策(IDM)所面临的挑战。作者提出了一个基础决策模型(FDM)的想法来克服这些挑战,并使IDM得到广泛采用。本文还展示了人工智能增强IDM潜在的各种方法和理论可行性。
Abstract:
The pervasive uncertainty and dynamic nature of real-world environments present significant challenges for the widespread implementation of machine-driven Intelligent Decision-Making (IDM) systems. Consequently, IDM should possess the ability to continuously … >>>
The pervasive uncertainty and dynamic nature of real-world environments present significant challenges for the widespread implementation of machine-driven Intelligent Decision-Making (IDM) systems. Consequently, IDM should possess the ability to continuously acquire new skills and effectively generalize across a broad range of applications. The advancement of Artificial General Intelligence (AGI) that transcends task and application boundaries is critical for enhancing IDM. Recent studies have extensively investigated the Transformer neural architecture as a foundational model for various tasks, including computer vision, natural language processing, and reinforcement learning. We propose that a Foundation Decision Model (FDM) can be developed by formulating diverse decision-making tasks as sequence decoding tasks using the Transformer architecture, offering a promising solution for expanding IDM applications in complex real-world situations. In this paper, we discuss the efficiency and generalization improvements offered by a foundation decision model for IDM and explore its potential applications in multi-agent game AI, production scheduling, and robotics tasks. Lastly, we present a case study demonstrating our FDM implementation, DigitalBrain (DB1) with 1.3 billion parameters, achieving human-level performance in 870 tasks, such as text generation, image captioning, video game playing, robotic control, and traveling salesman problems. As a foundation decision model, DB1 represents an initial step toward more autonomous and efficient real-world IDM applications. <<<
翻译
509.
muton (2023-05-31 22:39):
# paper:Challenging the Classical View: Recognition of Identity and Expression as Integrated Processes. https://doi.org/10.3390/ brainsci13020296 最近神经影像学的证据挑战了以往关于人脸信息特征和面部表情由不同神经通路分别加工处理的经典观点,而是认为身份和表情的信息在共同的脑区被编码。作者基于这一背景利用深度卷积神经网络分别对面孔身份和面孔表情的数据集进行了训练,结果发现各自训练后的神经网络不仅可以分别很好的解码身份/表情,同时对于解码未训练过的表情/身份时也有较好的表现。这一结果验证了上述假设。
IF:2.700Q3 Brain sciences, 2023-Feb-10. DOI: 10.3390/brainsci13020296 PMID: 36831839
Abstract:
Recent neuroimaging evidence challenges the classical view that face identity and facial expression are processed by segregated neural pathways, showing that information about identity and expression are encoded within common … >>>
Recent neuroimaging evidence challenges the classical view that face identity and facial expression are processed by segregated neural pathways, showing that information about identity and expression are encoded within common brain regions. This article tests the hypothesis that integrated representations of identity and expression arise spontaneously within deep neural networks. A subset of the CelebA dataset is used to train a deep convolutional neural network (DCNN) to label face identity (chance = 0.06%, accuracy = 26.5%), and the FER2013 dataset is used to train a DCNN to label facial expression (chance = 14.2%, accuracy = 63.5%). The identity-trained and expression-trained networks each successfully transfer to labeling both face identity and facial expression on the Karolinska Directed Emotional Faces dataset. This study demonstrates that DCNNs trained to recognize face identity and DCNNs trained to recognize facial expression spontaneously develop representations of facial expression and face identity, respectively. Furthermore, a congruence coefficient analysis reveals that features distinguishing between identities and features distinguishing between expressions become increasingly orthogonal from layer to layer, suggesting that deep neural networks disentangle representational subspaces corresponding to different sources. <<<
翻译
510.
(2023-05-31 22:30):
#paper Short communication: Dietary bovine milk–derived exosomes improve bone health in an osteoporosis-induced mouse model.DOI: 10.3168/jds.2019-17501. Yun等研究了牛初乳来源的外泌体在体外和体内是否可以促进抗骨质疏松症。抗酒石酸酸性磷酸酶染色的细胞在用外泌体处理过的Raw264.7细胞中受到了显著抑制,这表明破骨细胞的分化减少。口服给予外泌体2个月后,使用糖皮质激素颗粒诱发小鼠的骨质疏松症。与未经外泌体处理的糖皮质激素诱导的骨质疏松实验组相比,外泌体处理的小鼠实验组的骨矿物质密度显著提高。此外,骨质疏松症小鼠的肠道菌群中乳酸杆菌含量降低,但是通过摄入外泌体可以有效地恢复肠道菌群的组成。结果表明,从牛初乳中分离出的外泌体可能是预防骨质疏松症、改善骨重塑和抑制骨吸收的潜在候选物。牛初乳外泌体可以用作预防骨质疏松症的发作。
IF:3.700Q2 Journal of dairy science, 2020-Sep. DOI: 10.3168/jds.2019-17501 PMID: 32622594
Abstract:
Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and fracture susceptibility. In an aged … >>>
Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and fracture susceptibility. In an aged society with increased life expectancy, the incidence rate of osteoporosis is also rapidly increasing. Inadequate nutrition may negatively influence bone metabolism. Recently, many studies have investigated the functionality of milk-derived exosomes, which play important roles in cell-to-cell communication. However, there are few reports of how milk-derived exosomes influence osteoblast proliferation and differentiation. Here, we determined whether bovine colostrum-derived exosomes promote anti-osteoporosis in vitro and in vivo. Tartrate-resistant acid phosphatase-stained cells were significantly inhibited in Raw264.7 cells treated with exosomes, indicating reduced osteoclast differentiation. We induced osteoporosis in mice using glucocorticoid pellets after orally administering exosomes for 2 mo. Interestingly, the bone mineral density of exosome-fed mouse groups was significantly improved compared with the glucocorticoid-induced osteoporosis group without exosome treatment. In addition, Lactobacillus were decreased in the gut microbiota community of osteoporosis-induced mice, but the gut microbiota community composition was effectively restored by exosome intake. Taken together, we propose that exosomes isolated from bovine colostrum could be a potential candidate for osteoporosis prevention, bone remodeling improvement, and inhibition of bone resorption. To our knowledge, this is the first time that a protective effect of milk exosomes against osteoporosis has been demonstrated in vivo. Our results strongly suggest that bovine colostrum exosomes might be used as a prophylaxis to prevent the onset of osteoporosis. Indeed, our results offer promising alternative strategies in the nutritional management of age-related bone complications. <<<
翻译
511.
周周复始 (2023-05-31 22:29):
#paper doi:https://doi.org/10.48550/arXiv.2201.00308. DiffuseVAE: Efficient, Controllable and High-Fidelity Generation from Low-Dimensional Latents.2022.目前扩散概率模型在几个有竞争性图像合成基准上产生最先进的结果,但缺乏低维、可解释的潜在空间,并且生成速度较慢。而变分自编码器(VAEs)通常具有低维潜在空间,但生成的样本质量较差。基于此本文提出了一种新的生成框架DiffuseVAE,它将VAE集成到扩散模型框架中,并利用它为扩散模型设计新的条件参数化。文章表明,所得到的模型为扩散模型配备了低维VAE推断潜在代码,可用于下游任务,如条件生成。
Abstract:
Diffusion probabilistic models have been shown to generate state-of-the-art results on several competitive image synthesis benchmarks but lack a low-dimensional, interpretable latent space, and are slow at generation. On the … >>>
Diffusion probabilistic models have been shown to generate state-of-the-art results on several competitive image synthesis benchmarks but lack a low-dimensional, interpretable latent space, and are slow at generation. On the other hand, standard Variational Autoencoders (VAEs) typically have access to a low-dimensional latent space but exhibit poor sample quality. We present DiffuseVAE, a novel generative framework that integrates VAE within a diffusion model framework, and leverage this to design novel conditional parameterizations for diffusion models. We show that the resulting model equips diffusion models with a low-dimensional VAE inferred latent code which can be used for downstream tasks like controllable synthesis. The proposed method also improves upon the speed vs quality tradeoff exhibited in standard unconditional DDPM/DDIM models (for instance, FID of 16.47 vs 34.36 using a standard DDIM on the CelebA-HQ-128 benchmark using T=10 reverse process steps) without having explicitly trained for such an objective. Furthermore, the proposed model exhibits synthesis quality comparable to state-of-the-art models on standard image synthesis benchmarks like CIFAR-10 and CelebA-64 while outperforming most existing VAE-based methods. Lastly, we show that the proposed method exhibits inherent generalization to different types of noise in the conditioning signal. For reproducibility, our source code is publicly available at this https URL. <<<
翻译
512.
张贝 (2023-05-31 22:23):
#paper Int J Med Inform. 2019 Oct;130:103940.  doi: 10.1016/j.ijmedinf.2019.07.019.Clinical decision support for therapeutic decision-making in cancer: A systematic review  包括支持性护理在内的癌症管理较为复杂,需要根据已发表的以及患者特异性数据做出适当的治疗决策。临床决策支持(CDS)或许是支持复杂决策的有效实施策略,尽管CDS是否能够改善治疗结局和患者结局尚不明确。因此,本文对CDS进行了系统回顾,以确定CDS用于支持临床癌症治疗决策。令人关注的结果包括CDS对诊疗过程的影响。10项研究符合纳入标准,研究设计、设置和干预存在差异。在衡量过程结局的九项研究中,有五项显示出显著的改善;在衡量患者结局的六项中,有四项显示出显著改善。所有纳入的研究都使用了临床实践指南提及的CDS。总之,CDS用于指导癌症治疗决策是一个尚待研究但很有前景的领域。
Abstract:
Cancer management, including supportive care, is complex and requires availability and synthesis of published and patient-specific data to make appropriate therapeutic decisions. Clinical decision support (CDS) may be an effective … >>>
Cancer management, including supportive care, is complex and requires availability and synthesis of published and patient-specific data to make appropriate therapeutic decisions. Clinical decision support (CDS) may be an effective implementation strategy to support complex decision making although it is unclear whether it improves process outcomes, patient outcomes or both in cancer settings. We therefore conducted a systematic review to identify CDS that have been used to support therapeutic decision making in clinical cancer settings. Outcomes of interest included the effect of CDS on the process, such as clinician's decision making and effect on patient outcomes. Ten studies met inclusion criteria, with variability in the study design, setting, and intervention. Of the nine studies that measured process outcomes, five demonstrated significant improvement; and of the six that measured patient outcomes, four demonstrated significant improvement. All included studies utilized CDS that were informed by clinical practice guidelines. In conclusion, CDS to guide cancer therapeutic decision making is an understudied but promising area. Further research is needed. <<<
翻译
513.
尹志 (2023-05-31 22:12):
#paper doi: https://doi.org/10.1016/j.drudis.2021.05.019 Drug Discovery Today, 2021, De novo molecular design and generative models. 文章是来自业界的Benevolent AI写的,对从头的分子设计进行了综述。主要从颗粒度的角度进行 了分类,讨论了atom based, fragment based, reaction based三种不同的分子表示的视角下分子设计的方法。对于分子设计中的优化方法,文章分为无梯度和基于梯度的方法进行讨论,前者主要集中在演化算法和群体智能算法,而后者则是目前基于深度生成模型的主流。文章还强调了该领域建立合适评价标准和benchmark的重要性,不过考虑到分子设计务实的属性,这里还有非常多亟待解决的问题。文章的总结的思路很清楚,但是这个领域的发展实在是太快太快,因此2021年的综述显然是太老了,最近几年基于各种深度生成模型的分子设计很多已经相当实用化,还是建议大家看最新的文章,当然这篇综述还是可以当做一条不错的线索的。
Abstract:
Molecular design strategies are integral to therapeutic progress in drug discovery. Computational approaches for de novo molecular design have been developed over the past three decades and, recently, thanks in … >>>
Molecular design strategies are integral to therapeutic progress in drug discovery. Computational approaches for de novo molecular design have been developed over the past three decades and, recently, thanks in part to advances in machine learning (ML) and artificial intelligence (AI), the drug discovery field has gained practical experience. Here, we review these learnings and present de novo approaches according to the coarseness of their molecular representation: that is, whether molecular design is modeled on an atom-based, fragment-based, or reaction-based paradigm. Furthermore, we emphasize the value of strong benchmarks, describe the main challenges to using these methods in practice, and provide a viewpoint on further opportunities for exploration and challenges to be tackled in the upcoming years. <<<
翻译
514.
大勇 (2023-05-31 22:11):
#paper doi: https://doi.org/10.1038/s41586-022-05443-0 Kim, R., Hashimoto, A., Markosyan, N. et al. Ferroptosis of tumour neutrophils causes immune suppression in cancer. Nature 612, 338–346 (2022). 该文章主要是对肿瘤相关中性粒,也叫做髓源性抑制细胞(PMN-MDSC)在抗肿瘤免疫中的作用进行了研究,PMN-MDSC中所产生的铁死亡相关脂质代谢产物,可以通过抑制T细胞等的增殖从而抑制肿瘤进展和免疫检查点抑制剂治疗疗效。
IF:50.500Q1 Nature, 2022-12. DOI: 10.1038/s41586-022-05443-0 PMID: 36385526
Abstract:
Ferroptosis is a non-apoptotic form of regulated cell death that is triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. Ferroptosis inducers have shown … >>>
Ferroptosis is a non-apoptotic form of regulated cell death that is triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. Ferroptosis inducers have shown considerable effectiveness in killing tumour cells in vitro, yet there has been no obvious success in experimental animal models, with the notable exception of immunodeficient mice. This suggests that the effect of ferroptosis on immune cells remains poorly understood. Pathologically activated neutrophils (PMNs), termed myeloid-derived suppressor cells (PMN-MDSCs), are major negative regulators of anti-tumour immunity. Here we found that PMN-MDSCs in the tumour microenvironment spontaneously die by ferroptosis. Although decreasing the presence of PMN-MDSCs, ferroptosis induces the release of oxygenated lipids and limits the activity of human and mouse T cells. In immunocompetent mice, genetic and pharmacological inhibition of ferroptosis abrogates suppressive activity of PMN-MDSCs, reduces tumour progression and synergizes with immune checkpoint blockade to suppress the tumour growth. By contrast, induction of ferroptosis in immunocompetent mice promotes tumour growth. Thus, ferroptosis is a unique and targetable immunosuppressive mechanism of PMN-MDSCs in the tumour microenvironment that can be pharmacologically modulated to limit tumour progression. <<<
翻译
515.
哪有情可长 (2023-05-31 21:59):
#paper doi.org/10.1007/s42994-023-00095-8 Chromatin accessibility landscapes revealed the subgenome-divergent regulation networks during wheat grain development,最近在学习ATAC-seq数据分析,想利用别人已经发表的数据对自己的文章能够更深入。该作者对小麦籽粒5,9,15,20天的小麦籽粒发育阶段的构建了全基因组染色质开放图谱以及基因表达图谱,并对小麦籽粒发育中关键转录因子的调控网络进行了解析,揭示了小麦籽粒发育中亚基因组的分化调控,同时发掘了共调控淀粉与蛋白合成的转录因子。
IF:4.600Q1 aBIOTECH, 2023-Mar. DOI: 10.1007/s42994-023-00095-8 PMID: 37220536
Abstract:
Development of wheat ( L) grain mainly depends on the processes of starch synthesis and storage protein accumulation, which are critical for grain yield and quality. However, the regulatory network … >>>
Development of wheat ( L) grain mainly depends on the processes of starch synthesis and storage protein accumulation, which are critical for grain yield and quality. However, the regulatory network underlying the transcriptional and physiological changes of grain development is still not clear. Here, we combined ATAC-seq and RNA-seq to discover the chromatin accessibility and gene expression dynamics during these processes. We found that the chromatin accessibility changes are tightly associated with differential transcriptomic expressions, and the proportion of distal ACRs was increased gradually during grain development. Specific transcription factor (TF) binding sites were enriched at different stages and were diversified among the 3 subgenomes. We further predicted the potential interactions between key TFs and genes related with starch and storage protein biosynthesis and found different copies of some key TFs played diversified roles. Overall, our findings have provided numerous resources and illustrated the regulatory network during wheat grain development, which would shed light on the improvement of wheat yields and qualities. <<<
翻译
516.
庞庞 (2023-05-31 16:12):
#paper doi:https://doi.org/10.1038/s41591-023-02317-4 A shared neural basis underlying psychiatric comorbidity 之前对于精神疾病共病程度,通常使用p因子衡量。但是,这种指标通过临床评分得到,和共病的神经底物、基因都没有关联。对此,作者提出了一种新的神经生物学的跨疾病精神因子:NP因子。作者通过将与多种精神疾病得分显著相关的脑网络连接进行并集,并筛除掉在纵向数据上不稳定的连接,从而获得NP因子。他们同时证明了,NP因子与神经解剖位置、行为以及基因的关系。最后,NP因子可以泛化到其他类型的数据集上,这对以后的精神疾病的干预提供了帮助。
IF:58.700Q1 Nature medicine, 2023-05. DOI: 10.1038/s41591-023-02317-4 PMID: 37095248
Abstract:
Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used a large longitudinal neuroimaging … >>>
Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used a large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) to define a neuropsychopathological (NP) factor across externalizing and internalizing symptoms using multitask connectomes. We demonstrate that this NP factor might represent a unified, genetically determined, delayed development of the prefrontal cortex that further leads to poor executive function. We also show this NP factor to be reproducible in multiple developmental periods, from preadolescence to early adulthood, and generalizable to the resting-state connectome and clinical samples (the ADHD-200 Sample and the Stratify Project). In conclusion, we identify a reproducible and general neural basis underlying symptoms of multiple mental health disorders, bridging multidimensional evidence from behavioral, neuroimaging and genetic substrates. These findings may help to develop new therapeutic interventions for psychiatric comorbidities. <<<
翻译
517.
Vincent (2023-05-31 13:56):
#paper doi: https://doi.org/10.1111/j.1467-9868.2008.00674.x Journal of he Royal Statistical Society, 2008, Sure independence screening for ultrahighdimensional feature space. 高维数据往往面临着两大难题,参数估计的准确性和计算负担。先前的方法(Dantzig selector)在处理极高维数据(log p > n)时还是不够有效,这篇文章提出了一种基于相关性学习的特征筛选方法,能够将数据从极高维降到的合适的维度(小于n)。文章展示了在十分普遍的渐进框架下,相关性学习有可靠的筛选性能。同时作为该方法的扩展,文章还提出了一种迭代式的特征筛选,能够在有限数据量的情况下,提高筛选的准确性。此外当使用该方法把高维数据降低到低维之后,其他变量选择的方法例如lasso等也可以被运用进来,从而实现更准确和更快速的变量选择。
Abstract:
SummaryVariable selection plays an important role in high dimensional statistical modelling which nowadays appears in many areas and is key to various scientific discoveries. For problems of large scale or … >>>
SummaryVariable selection plays an important role in high dimensional statistical modelling which nowadays appears in many areas and is key to various scientific discoveries. For problems of large scale or dimensionality p, accuracy of estimation and computational cost are two top concerns. Recently, Candes and Tao have proposed the Dantzig selector using L1-regularization and showed that it achieves the ideal risk up to a logarithmic factor log(p). Their innovative procedure and remarkable result are challenged when the dimensionality is ultrahigh as the factor log(p) can be large and their uniform uncertainty principle can fail. Motivated by these concerns, we introduce the concept of sure screening and propose a sure screening method that is based on correlation learning, called sure independence screening, to reduce dimensionality from high to a moderate scale that is below the sample size. In a fairly general asymptotic framework, correlation learning is shown to have the sure screening property for even exponentially growing dimensionality. As a methodological extension, iterative sure independence screening is also proposed to enhance its finite sample performance. With dimension reduced accurately from high to below sample size, variable selection can be improved on both speed and accuracy, and can then be accomplished by a well-developed method such as smoothly clipped absolute deviation, the Dantzig selector, lasso or adaptive lasso. The connections between these penalized least squares methods are also elucidated. <<<
翻译
518.
James (2023-05-30 15:22):
#paper doi: 10.1007/s00125-023-05930-7. Prediabetes, intervening diabetes and subsequent risk of dementia: the Atherosclerosis Risk in Communities (ARIC) study 这项研究主要是评估糖尿病前期与痴呆症的关联是否可以通过干预糖尿病的发作来解释。在社区动脉粥样硬化风险 (ARIC) 研究的参与者中,作者将基线糖尿病前期定义为 HbA1c 39-46 mmol/mol (5.7-6.4%),并将随后发生的糖尿病定义为自我报告的医生诊断或使用糖尿病药物并通过主动监测和确定是否患有痴呆。 作者对糖尿病与痴呆风险之间的关联进行了量化并评估了糖尿病诊断时的年龄是否改变了痴呆症的风险。结果表明糖尿病前期与痴呆症风险相关联,风险可以用随后发生的糖尿病来解释。 较早患糖尿病会大大增加痴呆症的风险。 预防或延缓前驱糖尿病向糖尿病的进展将减轻痴呆负担。
IF:8.400Q1 Diabetologia, 2023-08. DOI: 10.1007/s00125-023-05930-7 PMID: 37221246
Abstract:
AIMS/HYPOTHESIS: The aim of this work was to evaluate whether the association of prediabetes with dementia is explained by the intervening onset of diabetes.METHODS: Among participants of the Atherosclerosis Risk … >>>
AIMS/HYPOTHESIS: The aim of this work was to evaluate whether the association of prediabetes with dementia is explained by the intervening onset of diabetes.METHODS: Among participants of the Atherosclerosis Risk in Communities (ARIC) study we defined baseline prediabetes as HbA1c 39-46 mmol/mol (5.7-6.4%) and subsequent incident diabetes as a self-reported physician diagnosis or use of diabetes medication. Incident dementia was ascertained via active surveillance and adjudicated. We quantified the association of prediabetes with dementia risk before and after accounting for the subsequent development of diabetes among ARIC participants without diabetes at baseline (1990-1992; participants aged 46-70 years). We also evaluated whether age at diabetes diagnosis modified the risk of dementia.RESULTS: Among 11,656 participants without diabetes at baseline, 2330 (20.0%) had prediabetes. Before accounting for incident diabetes, prediabetes was significantly associated with the risk of dementia (HR 1.12 [95% CI 1.01, 1.24]). After accounting for incident diabetes, the association was attenuated and non-significant (HR 1.05 [95% CI 0.94, 1.16]). Earlier age of onset of diabetes had the strongest association with dementia: HR 2.92 (95% CI 2.06, 4.14) for onset before 60 years; HR 1.73 (95% CI 1.47, 2.04) for onset at 60-69 years; and HR 1.23 (95% CI 1.08, 1.40) for onset at 70-79 years.CONCLUSIONS/INTERPRETATION: Prediabetes is associated with dementia risk but this risk is explained by the subsequent development of diabetes. Earlier age of onset of diabetes substantially increases dementia risk. Preventing or delaying progression of prediabetes to diabetes will reduce dementia burden. <<<
翻译
519.
张浩彬 (2023-05-30 11:48):
#paper:doi:10.48550/arXiv.2010.04515 Principal Component Analysis using Frequency Components of Multivariate Time Series 提出了一个新的谱分解方法,使得对多元时间序列(二阶平稳,宽平稳)进行分解,从而使得分解后的子序列在组内是有非零的谱相关,而跨组的子序列则具有零的谱相关性。从写作上,则是典型的问题引入,方法介绍、理论的渐近性质证明,数值模拟,实证研究,其中有大量的推导。
Abstract:
Dimension reduction techniques for multivariate time series decompose the observed series into a few useful independent/orthogonal univariate components. We develop a spectral domain method for multivariate second-order stationary time series … >>>
Dimension reduction techniques for multivariate time series decompose the observed series into a few useful independent/orthogonal univariate components. We develop a spectral domain method for multivariate second-order stationary time series that linearly transforms the observed series into several groups of lower-dimensional multivariate subseries. These multivariate subseries have non-zero spectral coherence among components within a group but have zero spectral coherence among components across groups. The observed series is expressed as a sum of frequency components whose variances are proportional to the spectral matrices at the respective frequencies. The demixing matrix is then estimated using an eigendecomposition on the sum of the variance matrices of these frequency components and its asymptotic properties are derived. Finally, a consistent test on the cross-spectrum of pairs of components is used to find the desired segmentation into the lower-dimensional subseries. The numerical performance of the proposed method is illustrated through simulation examples and an application to modeling and forecasting wind data is presented. <<<
翻译
520.
白鸟 (2023-05-30 09:20):
#paper https://doi.org/10.1093/nar/gkaa1027 Open Targets Platform: supporting systematic drug–target identification and prioritisation 1.靶标-疾病知识库: (1)20 个不同数据源的靶标-疾病关系的证据; (2)关键数据集的新证据:全基因组CRISPR敲除筛选数据, GWAS/UK BioBank统计遗传分析证据; (3)已知药物不良信息:上市后药物不良反应的评估,以及有关靶标成药性和安全性的新精选信息; 2.改进证据评分: 改进了证据评分框架以改进靶标识别 3.Open Targets平台开发: 更新10个版本,开发了用户界面和后端技术以提高性能和可用性
IF:16.600Q1 Nucleic acids research, 2021-01-08. DOI: 10.1093/nar/gkaa1027 PMID: 33196847
Abstract:
The Open Targets Platform (https://www.targetvalidation.org/) provides users with a queryable knowledgebase and user interface to aid systematic target identification and prioritisation for drug discovery based upon underlying evidence. It is … >>>
The Open Targets Platform (https://www.targetvalidation.org/) provides users with a queryable knowledgebase and user interface to aid systematic target identification and prioritisation for drug discovery based upon underlying evidence. It is publicly available and the underlying code is open source. Since our last update two years ago, we have had 10 releases to maintain and continuously improve evidence for target-disease relationships from 20 different data sources. In addition, we have integrated new evidence from key datasets, including prioritised targets identified from genome-wide CRISPR knockout screens in 300 cancer models (Project Score), and GWAS/UK BioBank statistical genetic analysis evidence from the Open Targets Genetics Portal. We have evolved our evidence scoring framework to improve target identification. To aid the prioritisation of targets and inform on the potential impact of modulating a given target, we have added evaluation of post-marketing adverse drug reactions and new curated information on target tractability and safety. We have also developed the user interface and backend technologies to improve performance and usability. In this article, we describe the latest enhancements to the Platform, to address the fundamental challenge that developing effective and safe drugs is difficult and expensive. <<<
翻译
回到顶部