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181.
尹志
(2024-07-31 15:46):
#paper Machine learning-aided generative molecular design, nature machine intelligence, DOI: 10.1038/s42256-024-00843-5. 文章综述了生成模型做分子设计领域的情况。从表征、生成方法和优化策略层面进行了总结,特别清楚。感兴趣的同学可以直接看文章里的几张表格,作为了解该领域发展情况及切入研究问题非常有帮助。
Abstract:
No abstract available.
182.
哪有情可长
(2024-07-31 15:18):
#paper Biofortification of iron content by regulating a NAC transcription factor in maize, Science, 7 Dec 2023, DOI: 10.1126/science.adf3256. 玉米籽粒铁的含量对人类健康具有重要的作用,该项研究发现一个NAC的转录因子能够提高籽粒中的Fe的含量,并且该基因能够在果仁基部胚乳转移层中富集表达,该蛋白可以直接调节铁转运体mRNA的丰度,并且该课题组也培育了富含铁元素的玉米品种。该项工作从GWAS找候选基因的流程,逻辑性强,一步步的验证该基因的确是籽粒富含铁的候选基因,这个方法可以借鉴。
Abstract:
Iron (Fe) deficiency remains widespread among people in developing countries. To help solve this problem, breeders have been attempting to develop maize cultivars with high yields and high Fe concentrations …
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Iron (Fe) deficiency remains widespread among people in developing countries. To help solve this problem, breeders have been attempting to develop maize cultivars with high yields and high Fe concentrations in the kernels. We conducted a genome-wide association study and identified a gene, (), that regulates Fe concentrations in maize kernels. We cultivated maize varieties with both high yield and high Fe concentrations in their kernels by using a molecular marker developed from a 42-base pair insertion or deletion (indel) in the promoter of . expression is enriched in the basal endosperm transfer layer of kernels, and the ZmNAC78 protein directly regulates messenger RNA abundance of Fe transporters. Our results thus provide an approach to develop maize varieties with Fe-enriched kernels.
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183.
徐炳祥
(2024-07-31 13:54):
#paper doi: 10.1101/2024.04.18.590148 bioRxiv, 2024, Droplet Hi-C for Fast and Scalable Profiling of Chromatin Architecture in Single Cells。单细胞Hi-C技术是目前单细胞三维基因组研究的主要技术手段,然而现有单细胞Hi-C技术存在通量不高,实验流程复杂,获取的单细胞文库质量较差等缺点。在本预印本论文中,作者们介绍了一种基于微流控技术的单细胞Hi-C技术的改良,称为Droplet Hi-C。Droplet Hi-C将单细胞Hi-C中barcoding步骤改为使用微流控平台自动化进行,从而大幅加快了文库构建的自动化水平和效率。Droplet Hi-C可实现超过4万个细胞的单细胞Hi-C文库的平行构建。借助此技术,作者分析了小鼠脑神经元中的染色质构象图谱的分布,研究了结直肠癌细胞系和组织中染色体外DNA的分布,实现了高通量的单细胞Hi-C和转录组共同构建。需要指出的是,论文仅提升了文库构建的效率,并未提升单个单细胞文库的质量,这可能是本领域下一个需要突破的重要技术瓶颈。
bioRxiv : the preprint server for biology,
2024-Apr-22.
DOI: 10.1101/2024.04.18.590148
PMID: 38712075
PMCID:PMC11071305
Abstract:
Comprehensive analysis of chromatin architecture is crucial for understanding the gene regulatory programs during development and in disease pathogenesis, yet current methods often inadequately address the unique challenges presented by …
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Comprehensive analysis of chromatin architecture is crucial for understanding the gene regulatory programs during development and in disease pathogenesis, yet current methods often inadequately address the unique challenges presented by analysis of heterogeneous tissue samples. Here, we introduce Droplet Hi-C, which employs a commercial microfluidic device for high-throughput, single-cell chromatin conformation profiling in droplets. Using Droplet Hi-C, we mapped the chromatin architecture at single-cell resolution from the mouse cortex and analyzed gene regulatory programs in major cortical cell types. Additionally, we used this technique to detect copy number variation (CNV), structural variations (SVs) and extrachromosomal DNA (ecDNA) in cancer cells, revealing clonal dynamics and other oncogenic events during treatment. We further refined this technique to allow for joint profiling of chromatin architecture and transcriptome in single cells, facilitating a more comprehensive exploration of the links between chromatin architecture and gene expression in both normal tissues and tumors. Thus, Droplet Hi-C not only addresses critical gaps in chromatin analysis of heterogeneous tissues but also emerges as a versatile tool enhancing our understanding of gene regulation in health and disease.
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184.
前进
(2024-07-31 11:35):
#paper DOI:https://doi.org/10.48550/arXiv.2006.16236 Katharopoulos A, Vyas A, Pappas N, et al. Transformers are rnns: Fast autoregressive transformers with linear attention[C]//International conference on machine learning. PMLR, 2020: 5156-5165.
这篇论文提出了一种新型的线性Transformer模型,该模型通过将自注意力机制表达为线性点积的核特征映射,并利用矩阵乘法的结合性质,显著降低了传统Transformer在处理长序列时的计算复杂度,从O(N^2)降低到O(N)。作者展示了这种新模型不仅能够实现与标准Transformer相似的性能,而且在自回归预测长序列时速度提升了多达4000倍。此外,论文还探讨了Transformer与循环神经网络(RNN)之间的关系,证明了通过适当的转换,Transformer可以像RNN一样高效地进行自回归预测。
arXiv,
2020-06-29T17:55:38Z.
DOI: 10.48550/arXiv.2006.16236
Abstract:
Transformers achieve remarkable performance in several tasks but due to theirquadratic complexity, with respect to the input's length, they areprohibitively slow for very long sequences. To address this limitation, weexpress …
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Transformers achieve remarkable performance in several tasks but due to theirquadratic complexity, with respect to the input's length, they areprohibitively slow for very long sequences. To address this limitation, weexpress the self-attention as a linear dot-product of kernel feature maps andmake use of the associativity property of matrix products to reduce thecomplexity from $\mathcal{O}\left(N^2\right)$ to $\mathcal{O}\left(N\right)$,where $N$ is the sequence length. We show that this formulation permits aniterative implementation that dramatically accelerates autoregressivetransformers and reveals their relationship to recurrent neural networks. Ourlinear transformers achieve similar performance to vanilla transformers andthey are up to 4000x faster on autoregressive prediction of very longsequences.
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185.
李翛然
(2024-07-30 20:10):
#paper DOI:10.1101/2023.08.08.552403 Identifying small-molecules binding sites in RNA conformational ensembles with SHAMAN 这篇文章怎么说呢,一看就是搞计算机人写的。我来说说为啥。
介绍了一种名为SHAMAN的计算技术,可以识别RNA结构集合中的潜在小分子结合位点。与依赖静态结构的其他计算工具不同,SHAMAN旨在解决RNA分子动态性带来的挑战。该技术通过分析RNA结构的构象集合,而不仅仅是单一静态结构,来识别潜在的结合位点。这种方法对于理解小分子与RNA柔性和动态性之间的相互作用特别有用。
这里面的关键点,是RNA的构象如何确定的,但是他是使用这个方法确定rna构象的:
1.使用分子动力学(MD)模拟来生成RNA的构象集合。论文中提到使用了Amber力场和TIP3P水模型进行了100 ns的MD模拟。
2.从MD轨迹中提取出具有代表性的RNA构象集合。作者使用了聚类算法来对MD轨迹进行聚类,选择了聚类中心作为代表性构象。
3. 这些代表性构象进行分析,识别小分子可能结合的位点。SHAMAN工具就是用来分析这些构象集合,预测小分子的可能结合位点。
这就很扯了, 用聚类的方法来选取最有可能的rna 结构,这不扯呢么! 邮箱TIP3P水模型就已经是生物容忍的最低限度了,居然在这个状态下模拟rna,然后用数学聚类的方法来选取构想。 有点扯!缺乏 实验室人员的嘲讽~~~哈哈
bioRxiv,
2024-2-28.
DOI: 10.1101/2023.08.08.552403
Abstract:
AbstractThe rational targeting of RNA with small molecules is hampered by our still limited understanding of RNA structural and dynamic properties. Mostin silicotools for binding site identification rely on static …
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AbstractThe rational targeting of RNA with small molecules is hampered by our still limited understanding of RNA structural and dynamic properties. Mostin silicotools for binding site identification rely on static structures and therefore cannot face the challenges posed by the dynamic nature of RNA molecules. Here, we present SHAMAN, a computational technique to identify potential small-molecule binding sites in RNA structural ensembles. SHAMAN enables exploring the conformational landscape of RNA with atomistic molecular dynamics and at the same time identifying RNA pockets in an efficient way with the aid of probes and enhanced-sampling techniques. In our benchmark composed of large, structured riboswitches as well as small, flexible viral RNAs, SHAMAN successfully identified all the experimentally resolved pockets and ranked them among the most favorite probe hotspots. Overall, SHAMAN sets a solid foundation for future drug design efforts targeting RNA with small molecules, effectively addressing the long-standing challenges in the field.
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186.
张浩彬
(2024-07-29 13:18):
#paper DOI: https://doi.org/10.1038/s41586-024-07566-y ,AI models collapse when trained on recursively generated data。Nature关于大模型合成语料的探讨文章,讨论了在训练数据中,合成语料的加入(可能是被动,由于现有网络资料已经大量的大模型合成语料),导致模型崩溃的问题。当然,合成语料的使用易燃是大模型的训练的有效方式,但是要做好对合成语料的筛选工作
Abstract:
AbstractStable diffusion revolutionized image creation from descriptive text. GPT-2 (ref. 1), GPT-3(.5) (ref. 2) and GPT-4 (ref. 3) demonstrated high performance across a variety of language tasks. ChatGPT introduced such …
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AbstractStable diffusion revolutionized image creation from descriptive text. GPT-2 (ref. 1), GPT-3(.5) (ref. 2) and GPT-4 (ref. 3) demonstrated high performance across a variety of language tasks. ChatGPT introduced such language models to the public. It is now clear that generative artificial intelligence (AI) such as large language models (LLMs) is here to stay and will substantially change the ecosystem of online text and images. Here we consider what may happen to GPT-{n} once LLMs contribute much of the text found online. We find that indiscriminate use of model-generated content in training causes irreversible defects in the resulting models, in which tails of the original content distribution disappear. We refer to this effect as ‘model collapse’ and show that it can occur in LLMs as well as in variational autoencoders (VAEs) and Gaussian mixture models (GMMs). We build theoretical intuition behind the phenomenon and portray its ubiquity among all learned generative models. We demonstrate that it must be taken seriously if we are to sustain the benefits of training from large-scale data scraped from the web. Indeed, the value of data collected about genuine human interactions with systems will be increasingly valuable in the presence of LLM-generated content in data crawled from the Internet.
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187.
盼盼
(2024-07-26 17:56):
#paper DOI: 10.1093/procel/pwae037 ,本研究报告了一项自体造血干细胞基因治疗(HSCGT)已发病的青少年型异染性脑白质营养不良(MLD)患者将近10年的安全性和有效性随访研究。该团队于2013年开创了亚洲首个造血干细胞基因疗法应用于有症状的青少年型MLD患者,随后进行了一项长期的多中心、开放临床试验,通过分析治疗后短期和长期随访期间发生的不良事件以评估该疗法的长期安全性,通过ARSA活性检测、MRI评分及神经功能评分等评估结果展示HSCGT 是安全的,使晚发型青年mld患者临床获益。
Abstract:
Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for …
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Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre- and early-symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early-onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with post-symptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over nine years. The most common adverse events (AEs) within two months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with post-symptomatic juvenile MLD.
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188.
颜林林
(2024-07-20 14:59):
#paper doi:10.1371/journal.pcbi.1012232, PLOS Computational Biology, Ten simple rules for building and maintaining a responsible data science workflow. “十条简单规则(Ten simple rules)” 是 PLOS Comp. Bio. 杂志上非常受欢迎的系列评论文章,每次篇幅不长,谈一个主题,提供十条“规则”并逐一展开解释,这些建议通常来自该领域有经验者,因此建议本身往往都非常简明且中肯,很值得阅读。这一篇说的是如何构建并维持“负责任”的数据科学流程,简单说其实就是“如何不作恶”,提到的建议包括提前考虑研究可能导致的恶性结果、注意数据源的偏差、经常性复盘和审视、迭代更新评估方法及标准、保持透明度等。像我们这种天天跟数据打交道的人,用这篇作为一张日常检查清单,也是不错的选择。
IF:3.800Q1
PLoS computational biology,
2024-Jul.
DOI: 10.1371/journal.pcbi.1012232
PMID: 39024267
PMCID:PMC11257324
Abstract:
No abstract available.
189.
龙海晨
(2024-07-08 09:45):
#paper Li X, Sun X, Li L, Luo Y, Chi Y, Zheng G. MDM2-mediated ubiquitination of LKB1 contributes to the development of diabetic cataract. Exp Cell Res. 2022 Aug 1;417(1):113191. doi: 10.1016/j.yexcr.2022.113191. Epub 2022 May 2. PMID: 35513074.糖尿病性白内障(Diabetic cataract,DC)是糖尿病的常见并发症。晶状体上皮细胞(lens epithelial cells , LEC)的上皮-间质转化(epithelial-mesenchymal transition, EMT)在DC发展中起关键作用。鼠双微体2(Murine double minute 2 ,MDM2)是一种E3泛素连接酶,通过调节多种靶点促进EMT。文章发现DC患者和大鼠晶状体中MDM2的mRNA和蛋白质水平上调。因此,构建了高糖(high glucose ,HG)诱导的人晶状体上皮细胞( human lens epithelial cells,HLEC)进行进一步研究。结果表明,HG培养的HLEC中MDM2水平升高,MDM2敲低减轻了HG诱导的异常迁移、EMT和氧化应激损伤。免疫共沉淀和泛素化试验表明,MDM2 通过泛素化降解下调了 LKB1 的表达。研究发现,LKB1 在人类和大鼠 DC 晶状体以及 HG 刺激的 HLEC 中表达较低。此外,LKB1 过表达减轻了 HG 诱导的 HLEC 功能障碍。研究数据显示,MDM2 敲低引起的 EMT 和氧化应激相关变化可以通过 LKB1 下调得到恢复。
IF:3.300Q2
Experimental cell research,
2022-08-01T00:00:00.
DOI: 10.1016/j.yexcr.2022.113191
PMID: 35513074
Abstract:
No abstract available.
190.
DeDe宝
(2024-07-05 17:12):
#paper doi:10.1016/j.cognition.2022.105126 Adaptive cognitive maps for curved surfaces in the 3D world 三维空间中,垂直信息大量存在,但之前大部分研究只聚焦于平面上的空间表征,构建2D认知地图。在该研究中, 研究者研究了人类是通过构建降维的扁平 2D 地图还是完整的 3D 地图来表示曲面。被试通过在表面的凹面上行驶(实验 1)、驾驶并垂直观察(实验 2)或飞行(实验 3)来了解虚拟环境中位于平面和曲面上的物体的位置。随后,他们被要求检索物体之间的路径距离或 3D 欧几里得距离。结果表明,被试明显低估曲线的路径距离,而接触3D结构更多的运动模式(飞行)改善了被试的估计表现。这些结果表明,被试在三维空间的认知地图不是2D的,也不是3D的,而是2D的流行表示,该认知地图可以根据经验和任务需求而调整。
3D世界中曲面的自适应认知地图
Abstract:
Terrains in a 3D world can be undulating. Yet, most prior research has exclusively investigated spatial representations on a flat surface, leaving a 2D cognitive map as the dominant model …
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Terrains in a 3D world can be undulating. Yet, most prior research has exclusively investigated spatial representations on a flat surface, leaving a 2D cognitive map as the dominant model in the field. Here, we investigated whether humans represent a curved surface by building a dimension-reduced flattened 2D map or a full 3D map. Participants learned the location of objects positioned on a flat and curved surface in a virtual environment by driving on the concave side of the surface (Experiment 1), driving and looking vertically (Experiment 2), or flying (Experiment 3). Subsequently, they were asked to retrieve either the path distance or the 3D Euclidean distance between the objects. Path distance estimation was good overall, but we found a significant underestimation bias for the path distance on the curve, suggesting an influence of potential 3D shortcuts, even though participants were only driving on the surface. Euclidean distance estimation was better when participants were exposed more to the global 3D structure of the environment by looking and flying. These results suggest that the representation of the 2D manifold, embedded in a 3D world, is neither purely 2D nor 3D. Rather, it is flexible and dependent on the behavioral experience and demand.
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3D 世界中的地形可能是起伏的。然而,大多数先前的研究都专门研究了平面上的空间表示,而 2D 认知地图是该领域的主要模型。在这里,我们研究了人类是否通过构建降维扁平化 2D 地图或完整的 3D 地图来表示曲面。参与者通过在表面的凹面驾驶(实验 1)、驾驶和垂直观察(实验 2)或飞行(实验 3)来学习在虚拟环境中放置在平面和曲面上的物体的位置。随后,他们被要求检索物体之间的路径距离或3D欧几里得距离。路径距离估计总体上是好的,但我们发现曲线上的路径距离存在明显的低估偏差,这表明即使参与者只是在表面上行驶,也可能存在潜在的3D捷径的影响。当参与者通过观察和飞行更多地暴露于环境的全球三维结构时,欧几里得距离估计更好。这些结果表明,嵌入在 3D 世界中的 2D 流形的表示既不是纯粹的 2D 也不是 3D。相反,它是灵活的,并依赖于行为经验和需求。
191.
小W
(2024-07-01 00:01):
#paper doi:10.1038/s41590-024-01828-7 The aged tumor microenvironment limits T cell control of cancer 这是一篇探索衰老微环境是如何影响癌症浸润CD8免疫细胞的文章,通过流式细胞术 和 scRNA-seq 等技术,发现了衰老促进肿瘤生长并改变 CD8+T 细胞的命运和功能,老年 TME 中的细胞外信号驱动诱导了一种不同于 典型细胞衰竭、进化保守的与年龄相关的功能障碍 CD8+ T 细胞状态(TTAD)。同时老年肿瘤小鼠无法从治疗性 mRNA 疫苗接种中受益,而重振 cDC1 的髓系靶向免疫疗法可以改善并增强老年小鼠的 CD8+ T 细胞的免疫能力。
老化的肿瘤微环境限制了T细胞对癌症的控制
Abstract:
The etiology and effect of age-related immune dysfunction in cancer is not completely understood. Here we show that limited priming of CD8 T cells in the aged tumor microenvironment (TME) …
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The etiology and effect of age-related immune dysfunction in cancer is not completely understood. Here we show that limited priming of CD8 T cells in the aged tumor microenvironment (TME) outweighs cell-intrinsic defects in limiting tumor control. Increased tumor growth in aging is associated with reduced CD8 T cell infiltration and function. Transfer of T cells from young mice does not restore tumor control in aged mice owing to rapid induction of T cell dysfunction. Cell-extrinsic signals in the aged TME drive a tumor-infiltrating age-associated dysfunctional (T) cell state that is functionally, transcriptionally and epigenetically distinct from canonical T cell exhaustion. Altered natural killer cell-dendritic cell-CD8 T cell cross-talk in aged tumors impairs T cell priming by conventional type 1 dendritic cells and promotes T cell formation. Aged mice are thereby unable to benefit from therapeutic tumor vaccination. Critically, myeloid-targeted therapy to reinvigorate conventional type 1 dendritic cells can improve tumor control and restore CD8 T cell immunity in aging.
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癌症中与年龄相关的免疫功能障碍的病因和影响尚不完全清楚。在这里,我们发现,在老年肿瘤微环境(TME)中,CD8 T细胞的有限启动超过了限制肿瘤控制的细胞内在缺陷。衰老过程中肿瘤生长增加与 CD8 T 细胞浸润和功能减少有关。由于T细胞功能障碍的快速诱导,从年轻小鼠转移T细胞并不能恢复老年小鼠的肿瘤控制。衰老 TME 中的细胞外源信号驱动肿瘤浸润、年龄相关的功能失调 (T) 细胞状态,该状态在功能、转录和表观遗传学上与经典 T 细胞耗竭不同。老年肿瘤中自然杀伤细胞-树突状细胞-CD8 T 细胞串扰的改变会损害传统 1 型树突状细胞对 T 细胞的启动并促进 T 细胞的形成。因此,老年小鼠无法从治疗性肿瘤疫苗接种中受益。至关重要的是,髓样靶向疗法使传统的 1 型树突状细胞恢复活力,可以改善肿瘤控制并在衰老中恢复 CD8 T 细胞免疫。
192.
林海onrush
(2024-07-01 00:00):
#paper, doi/10.5555/3600270.3602181. The Policy-gradient Placement and Generative Routing Neural Networks for Chip Design, 这篇论文提出了一种结合策略梯度强化学习模型和条件生成模型的新方法,用于VLSI芯片设计中的混合尺寸宏单元布置和路由。通过一个纯粹的神经网络管道,该方法能够高效地处理布置和路由任务,不依赖传统的启发式解算器。实验结果表明,该方法在减少布置重叠面积和生成准确路由方面表现优异,具有较高的成本效益。该研究展示了AI驱动的布置和路由方法在电子设计自动化中的潜力。
用于芯片设计的策略梯度放置和生成路由神经网络
Abstract:
No abstract available.
193.
钟鸣
(2024-06-30 23:55):
#paper The postfeminist entrepreneurial self and the platformisation of labour: A case study of yesheng female lifestyle bloggers on Xiaohongshu doi:10.1177/2059436422109589
这是一篇充满浓郁女性特色的学术论文:一个女性作者采访了8位女性博主,所在的平台(小红书)也是以女性为主要用户。作者访谈了8位博主,主要关注的问题是选择这份工作的动机(兴趣、社会对女性“顾家”的期待),以及在MCN背景下(平台劳动)受到的桎梏。文章的层次和条理不是很明确,更像是一篇采访后的随笔。文章篇幅不长但是洋洋洒洒,通过阅读这么一篇文章可以对后女权主义、消费主义、创业主义和新自由主义都有一定认识,管中窥豹。
194.
小年
(2024-06-30 23:17):
#paper The complete sequence and comparative analysis of ape sex chromosomes. Nature. 2024 Jun 13. doi: 10.1038/s41586-024-07473-2.
在本篇文章中,作者通过对五种大猿(倭黑猩猩、黑猩猩、西部低地大猩猩、婆罗洲猩猩和苏门答腊猩猩)和一种小猿(长臂猿)的X和Y染色体进行了端到端(T2T)无间隙组装,并对其性染色体的结构和进化进行了详细分析。研究发现,Y染色体在大小、序列对齐度和结构重排方面存在显著变异,而X染色体则相对更为稳定。具体来说,Y染色体在不同物种间的大小从30 Mb到68 Mb不等,而X染色体的大小范围较小,约为154 Mb到178 Mb。Y染色体表现出大量的结构重排,如倒位和插入,这些重排与基因功能的进化密切相关。此外,研究还发现Y染色体的放大区和倒位重复区显著扩展,并在不同物种中表现出快速进化。
阅读思考:这项研究通过对多个大猿物种的性染色体进行无间隙组装,极大地丰富了我们对灵长类动物性染色体结构和进化的理解。特别是,研究揭示了Y染色体的高度变异性和快速进化特征,这对于理解灵长类动物的性别决定和生殖生物学具有重要意义。此外,这些高质量的参考基因组为濒危的非人类大猿的保护提供了宝贵的遗传信息。然而,该研究的一个限制是其主要依赖于短读和长读测序数据,可能对某些高度重复区域的准确性有所不足。未来的研究应结合更多的高覆盖度长读测序技术,以提供更全面和精确的性染色体数据,从而更好地服务于灵长类动物的进化研究和保护基因组学。此外,扩大研究物种的范围,特别是包含更多的灵长类物种,将有助于全面理解性染色体的进化模式和功能多样性
Abstract:
Apes possess two sex chromosomes-the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions …
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Apes possess two sex chromosomes-the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions being linked to infertility. The X chromosome is vital for reproduction and cognition. Variation in mating patterns and brain function among apes suggests corresponding differences in their sex chromosomes. However, owing to their repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (bonobo (Pan paniscus), chimpanzee (Pan troglodytes), western lowland gorilla (Gorilla gorilla gorilla), Bornean orangutan (Pongo pygmaeus) and Sumatran orangutan (Pongo abelii)) and a lesser ape (the siamang gibbon (Symphalangus syndactylus)), and untangled the intricacies of their evolution. Compared with the X chromosomes, the ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements-owing to the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements and satellites. Many Y chromosome genes expand in multi-copy families and some evolve under purifying selection. Thus, the Y chromosome exhibits dynamic evolution, whereas the X chromosome is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of more than 100 individual great apes. These reference assemblies are expected to inform human evolution and conservation genetics of non-human apes, all of which are endangered species.
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195.
白鸟
(2024-06-30 23:11):
#paper http://doi.org/10.1126/science.abg4696,Developmental and evolutionary dynamics ofcis-regulatory elements in mouse cerebellar cells, science, 2021. 文章系统的揭示了小鼠小脑中细胞从早期神经发生到成年发育的顺式调控元件调控机制。该文章提供了scATAC数据和代码,很清晰地分析思路,很值得初学者学习和借鉴。
Abstract:
Organ development is orchestrated by cell- and time-specific gene regulatory networks. In this study, we investigated the regulatory basis of mouse cerebellum development from early neurogenesis to adulthood. By acquiring …
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Organ development is orchestrated by cell- and time-specific gene regulatory networks. In this study, we investigated the regulatory basis of mouse cerebellum development from early neurogenesis to adulthood. By acquiring snATAC-seq (single-nucleus assay for transposase accessible chromatin using sequencing) profiles for ~90,000 cells spanning 11 stages, we mapped cerebellar cell types and identified candidate cisregulatory elements (CREs). We detected extensive spatiotemporal heterogeneity among progenitor cells and a gradual divergence in the regulatory programs of cerebellar neurons during differentiation. Comparisons to vertebrate genomes and snATAC-seq profiles for ∼20,000 cerebellar cells from the marsupial opossum revealed a shared decrease in CRE conservation during development and differentiation as well as differences in constraint between cell types. Our work delineates the developmental and evolutionary dynamics of gene regulation in cerebellar cells and provides insights into mammalian organ development.
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196.
符毓 Yu
(2024-06-30 23:02):
#paper doi.org/10.48550/arXiv.2404.17569, 2024, MaPa: Text-driven Photorealistic Material Painting for 3D Shapes. 本文提供了通过文字给3D模型渲染高质量材质表面的算法。
算法分为四步,首先,将网格分解为不同的片段,并使用片段控制图像生成技术(具体采用 ControlNet)将它们投影到 2D 图像上;第二,根据相似的材质属性和外观将这些片段分类。第三,每个材质组都会经过选择过程,会在此过程中识别和优化合适的材质图,以准确表示其纹理和特性。最后是迭代的,不断在多个视图中渲染和优化这些材质图,填补视觉数据中的任何空白,并重复分组和优化阶段,直到网格的每个片段都由相应的材质图准确表示。这种综合方法可确保根据 3D 网格每个片段的独特特征定制详细而逼真的材质纹理。
arXiv,
2024.
DOI: 10.48550/arXiv.2404.17569
Abstract:
This paper aims to generate materials for 3D meshes from text descriptions.Unlike existing methods that synthesize texture maps, we propose to generatesegment-wise procedural material graphs as the appearance representation, whichsupports …
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This paper aims to generate materials for 3D meshes from text descriptions.Unlike existing methods that synthesize texture maps, we propose to generatesegment-wise procedural material graphs as the appearance representation, whichsupports high-quality rendering and provides substantial flexibility inediting. Instead of relying on extensive paired data, i.e., 3D meshes withmaterial graphs and corresponding text descriptions, to train a material graphgenerative model, we propose to leverage the pre-trained 2D diffusion model asa bridge to connect the text and material graphs. Specifically, our approachdecomposes a shape into a set of segments and designs a segment-controlleddiffusion model to synthesize 2D images that are aligned with mesh parts. Basedon generated images, we initialize parameters of material graphs and fine-tunethem through the differentiable rendering module to produce materials inaccordance with the textual description. Extensive experiments demonstrate thesuperior performance of our framework in photorealism, resolution, andeditability over existing methods. Project page: https://zju3dv.github.io/MaPa
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197.
庞庞
(2024-06-30 23:01):
#paper Personalized brain circuit scores identify clinically distinct biotypes in depression and anxiety DOI: 10.1038/s41591-024-03057-9 本文基于作者提出的静息态以及任务态功能网络的指标,对1000多个抑郁症患者进行了亚型的分类,分出来六个亚型,这六个亚型存在行为、临床量表以及对治疗反应的差异,可以更好的进行精准化医疗。
Abstract:
There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or 'biotypes' to enable stratification of patients with depression and anxiety. We used task-free and task-evoked …
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There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or 'biotypes' to enable stratification of patients with depression and anxiety. We used task-free and task-evoked data from a standardized functional magnetic resonance imaging protocol conducted across multiple studies in patients with depression and anxiety when treatment free (n = 801) and after randomization to pharmacotherapy or behavioral therapy (n = 250). From these patients, we derived personalized and interpretable scores of brain circuit dysfunction grounded in a theoretical taxonomy. Participants were subdivided into six biotypes defined by distinct profiles of intrinsic task-free functional connectivity within the default mode, salience and frontoparietal attention circuits, and of activation and connectivity within frontal and subcortical regions elicited by emotional and cognitive tasks. The six biotypes showed consistency with our theoretical taxonomy and were distinguished by symptoms, behavioral performance on general and emotional cognitive computerized tests, and response to pharmacotherapy as well as behavioral therapy. Our results provide a new, theory-driven, clinically validated and interpretable quantitative method to parse the biological heterogeneity of depression and anxiety. Thus, they represent a promising approach to advance precision clinical care in psychiatry.
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198.
muton
(2024-06-30 23:00):
#paper Alagapan, S., Choi, K. S., Heisig, S., Riva-Posse, P., Crowell, A., Tiruvadi, V., Obatusin, M., Veerakumar, A., Waters, A. C., Gross, R. E., Quinn, S., Denison, L., O'Shaughnessy, M., Connor, M., Canal, G., Cha, J., Hershenberg, R., Nauvel, T., Isbaine, F., Afzal, M. F., … Rozell, C. J. (2023). Cingulate dynamics track depression recovery with deep brain stimulation. Nature, 622(7981), 130–138. https://doi.org/10.1038/s41586-023-06541-3 扣带下扣带回(SCC)的脑深部刺激(DBS)可以为难治性抑郁症(TRD)提供长期的症状缓解,但是不一定能够实现稳定的康复,但是作者使用了一种新的设备叫做SCC DBS,记录了抑郁症患者24周的治疗成果,结果发现90%的患者表现出了稳定的临床响应,70%的患者症状达到缓解。用其中6个人的局部场电位结合AI可以达到识别SCC局部场电位变化进而预测病人当下的临床状态。总体来说,作者使用一种新的电刺激技术和手段大幅成功治愈了抑郁症患者,且发现了抑郁状态的神经指标。
Abstract:
Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD). However, achieving stable recovery is unpredictable, typically requiring trial-and-error stimulation adjustments due …
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Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD). However, achieving stable recovery is unpredictable, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.
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199.
前进
(2024-06-30 22:29):
#paper Liu R , Li Z , Fan X ,et al.Learning Deformable Image Registration from Optimization: Perspective, Modules, Bilevel Training and Beyond[J]. 2020.DOI:10.48550/arXiv.2004.14557.
论文提出了一个新的基于深度学习的框架,旨在通过多尺度传播优化微分同胚模型来整合传统变形配准方法和基于深度学习的方法的优势,并避免它们的局限性。具体来说,作者提出了一个通用的优化模型来解决微分同胚配准问题,并开发了一系列可学习的架构,以从粗到细的学习图像特征完成配准。此外,论文还提出了一种新颖的双层自调整训练策略,允许高效地搜索任务特定的超参数,这增加了对各种类型数据的灵活性,同时减少了计算和人力负担。
作者多种数据集上进行了配准实验,包括大脑MRI数据的图像到图谱配准和肝脏CT数据的图像到图像配准。实验结果表明,所提出的方法在保持微分同胚的同时,达到了最先进的性能。此外,作者还将其框架应用于多模态图像配准,并研究了其配准如何支持医学图像分析的下游任务,包括多模态融合和图像分割。
arXiv,
2020.
DOI: 10.48550/arXiv.2004.14557
Abstract:
Conventional deformable registration methods aim at solving an optimizationmodel carefully designed on image pairs and their computational costs areexceptionally high. In contrast, recent deep learning based approaches canprovide fast deformation …
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Conventional deformable registration methods aim at solving an optimizationmodel carefully designed on image pairs and their computational costs areexceptionally high. In contrast, recent deep learning based approaches canprovide fast deformation estimation. These heuristic network architectures arefully data-driven and thus lack explicit geometric constraints, e.g.,topology-preserving, which are indispensable to generate plausibledeformations. We design a new deep learning based framework to optimize adiffeomorphic model via multi-scale propagation in order to integrateadvantages and avoid limitations of these two categories of approaches.Specifically, we introduce a generic optimization model to formulatediffeomorphic registration and develop a series of learnable architectures toobtain propagative updating in the coarse-to-fine feature space. Moreover, wepropose a novel bilevel self-tuned training strategy, allowing efficient searchof task-specific hyper-parameters. This training strategy increases theflexibility to various types of data while reduces computational and humanburdens. We conduct two groups of image registration experiments on 3D volumedatasets including image-to-atlas registration on brain MRI data andimage-to-image registration on liver CT data. Extensive results demonstrate thestate-of-the-art performance of the proposed method with diffeomorphicguarantee and extreme efficiency. We also apply our framework to challengingmulti-modal image registration, and investigate how our registration to supportthe down-streaming tasks for medical image analysis including multi-modalfusion and image segmentation.
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200.
尹志
(2024-06-30 17:56):
#paper DOI: 10.1038/s41534-017-0048-9 Coherent Ising machines—optical neural networks operating at the quantum limit. npj Quantum Inf 3, 49 (2017). 这个工作介绍了一种新型的量子计算方案,相干ising机(CIM)。区别于传统的量子计算方案,CIM有着特别的实用优势,比如对退相干时间没有要求。当然这和它的设计思路相关。从2011年理论方案出现,到目前真机落地的发展,其基本的原理没有变化,区别于传统量子计算在叠加态下进行逻辑计算,再统一进行readout的操作,CIM一开始就采取迭代读取的方式,在每一轮计算(演化)后,进行读读取测量,对系统状态(比如相位情况)进行计算反馈,从而在足够的迭代次数后获得保真度较高的计算结果。该方案特别适合目前的各类优化问题的解决,如果将传统的量子计算方案(量子电路为主)看成瀑布流的开发思路,那么CIM应该就是迭代的敏捷开发。CIM确实是很有意思的想法,希望能够在这个量子计算范式下结合AI做一些有意思的探索。
Abstract:
AbstractIn this article, we will introduce the basic concept and the quantum feature of a novel computing system, coherent Ising machines, and describe their theoretical and experimental performance. We start …
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AbstractIn this article, we will introduce the basic concept and the quantum feature of a novel computing system, coherent Ising machines, and describe their theoretical and experimental performance. We start with the discussion how to construct such physical devices as the quantum analog of classical neuron and synapse, and end with the performance comparison against various classical neural networks implemented in CPU and supercomputers.
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