当前共找到 1188 篇文献分享,本页显示第 741 - 760 篇。
741.
半面阳光
(2022-11-12 18:32):
#paper DOI: 10.1126/science.35.896.340 Science, 1912, First use of word “genotype”. 这篇文章1921年3月1日发表在Science杂志,是一篇Letter,作者Henry Fairfield Osborn。文章非常短,只有几百字。主要内容是讨论“genotype”这个词的使用起源。作者向当时的一位权威命名学和分类学家Dr Joel Asaph Allen询问“genotype”这个词首次被使用的情形。Dr Joel Asaph Allen回复说他认为genotype这个词最早使用是在1903年,并且在1910年之前获得了国际动物学委员会(International Zoological Commission)官方认可,最早应该是被Nature或Annals and magazine of Natural History杂志的作者所用。Genotype词源于希腊语的两个词,语义是“kind, genus” 和“type”。这个合成词中间用“O”这个元音进行连接。但是作者提出为什么没有像genetic和genesis一样用元音“E”来连接呢?作者提出理清“genotype”一词的使用问题,可以避免后续使用中可能出现的混淆情况。这篇Letter类似“社交媒体”类的分享,感觉很像1900年代的朋友圈。因为本文的信息量太少,原文中有些内容读起来有点一头雾水。根据文章提到的一些人和概念,去回溯了几篇文章,发现当时对“Genotype”这个词的使用似乎很有争议,类似于引发了一波当时的“骂战”。1921年3月29日的Science杂志的Letter版块,又有一篇名为The use of the word “genotype”的文章,讨论学术界对这个词使用中的不同意见。另外,这个词还引出了一个对遗传学发展有重要影响的人Wilhelm Ludvig Johannsen,他被认为是Gene、Genotype、Phenotype这些概念的创造者,以及遗传学科的奠基人之一。在双螺旋结构发现之前,遗传学领域的发展和历史应该很热闹,只是课本以及平时工作研究所看的文献中,很少有机会读到这种更偏向于生物学历史研究的文章。另外,这个作者Henry Fairfield Osborn除了是一个著名的古生物学者,担任美国自然历史博物馆馆长达25年,还是个富二代,他的父亲是当时著名的铁路大亨William Henry Osborn。
Abstract:
No abstract available.
742.
张浩彬
(2022-11-10 00:03):
#paper Momentum Contrast for Unsupervised Visual Representation Learning
doi:10.1109/cvpr42600.2020.00975
大名鼎鼎的moco。之前只是粗略了解,今天算是认真精读了一下。受nlp的影响,cv也开始了自监督方法的新一代卷了。
自监督,其实也是无监督了。倒是为了和前人分开,又起了self supervised learning的名字。moco这篇论文,算是趟平了有监督和无监督的差距了,第一次用无监督的方法取得了比有监督预训练任务更好的结果。毕竟人工打标签还是很贵的,如果可以利用无监督的方法对模型进行预训练,那么可以说大大降低了受限于标注数据的性能瓶颈了。
说回本文的技术,可以算是自监督目前的一个主流了(另一个是生成式)。在对比学习中,关键在于:1代理任务;2损失函数。当然本文的突出主要贡献还是在于动量更新方法。
1.moco中的代理任务,选择了比较简单的个体判别,即对于原始数据某个样本x_i,通过两个不同的数据增强,获得锚点样本和正样本;而其他样本,则是相对于该基础样本的负样本。另外,作者提到,把锚点称之为q(query),正样本和负样本对称之为k(key)。
2.损失函数是infonce,本质是其实还是类似于softmax。但是考虑到我们有这么多负样本,实际上就有这么多类别,所以选用了infonce,超参数是“温度”
3.接下里是本文的两个贡献,或者说回归对比学习,作者也提到受到两个问题制约:1是字典大小;2是字典一致性(字典姑且理解为负样本集,对比学习中,负样本集越大越好。另外moco是一个正样本,但也有文献证明,使用多个正样本更好)。(1)字典大小问题:在simclr这样的方法中,实际上每个batch都是对应的字典,这样就保证字典一致性,但是问题是字典大小受限制。要对这么多一个字典是反向传播,需要GPU非常大的内存,其次就是大batchsize的优化,相对也更难。(2)字典一致性问题:相比于simclr这样的端到端方法,另一个套路是使用memory bank的方式。我们依然有一个很大的字典,每次从字典抽样k个负样本进行梯度更新。但是这样的问题在于每次我们只更新了抽样的k个样本,实际上,这时候整个字典的特征是很不一致的(因为我们每次用一个较大梯度去更新所选k个样本,这样对于一个大字典,一个epoch后,第一次更新和最后一次更新的特征会差别很大)
4.针对以上问题,作者首先提出队列作为字典。即每次更新新的特征后,最久的特征剔除出字典,新的特征进度。
5.其次就是动量更新。及我们依然使用梯度下降更新q的encoder。但是我们不再使用梯度更新更细k的encoder,而是使用动量的方式,即,(另外,初始化时,k的encoder是直接复制q的encoder)并且m选择一个非常大的数,例如0.999,这就保证了每次更新都只更新一点,从而保证了字典一致性。
5.接下里是下游任务实现。作者冻结了主干网络,之后只使用了Linear Classification Protocol(一个全连接层和softmax层)作为最后的分类器,与经过ImageNet预训练后的其他模型进行比较,除少部分任务外,moco基本都取得了sota结果。
6.另一个有意思的地方是,moco的分类器,用girdsearch日常搜索发现最优的学习率是30.作者解释到,这也说明了自监督得到的特征确实与有监督得到的特征差别很大。另外在后续比较中,考虑到使用grid search不方便,作者使用了归一化处理。
Abstract:
We present Momentum Contrast (MoCo) for unsupervised visual representation learning. From a perspective on contrastive learning as dictionary look-up, we build a dynamic dictionary with a queue and a moving-averaged …
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We present Momentum Contrast (MoCo) for unsupervised visual representation learning. From a perspective on contrastive learning as dictionary look-up, we build a dynamic dictionary with a queue and a moving-averaged encoder. This enables building a large and consistent dictionary on-the-fly that facilitates contrastive unsupervised learning. MoCo provides competitive results under the common linear protocol on ImageNet classification. More importantly, the representations learned by MoCo transfer well to downstream tasks. MoCo can outperform its supervised pre-training counterpart in 7 detection/segmentation tasks on PASCAL VOC, COCO, and other datasets, sometimes surpassing it by large margins. This suggests that the gap between unsupervised and supervised representation learning has been largely closed in many vision tasks.
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743.
龙海晨
(2022-11-01 23:04):
#paper Vicente M, Schlebusch C M. African population history: an ancient DNA perspective[J]. Current Opinion in Genetics & Development, 2020, 62: 8-15. PMID: 32563853 DOI: 10.1016/j.gde.2020.05.008
上次我分享了基因和考古相关的一篇实验论著,结果几天后公布的诺贝尔奖和这项技术相关。发现群里不少人对这个方向感兴趣。这次给大家推荐一篇综述。这篇综述所涉及的领域就是通过一个古老的DNA视角去看非洲的人口历史。如果对于基因考古感兴趣的朋友,除了这篇综述之外,该综述的参考文献也推荐阅读。这篇文章通过总结相关的研究文献。通过研究非洲大陆现代人类,古代人类,远古人类的遗传基因,与考古发现相关联对比,研究非洲大陆从狩猎采集到农耕文明以及现代的文明发展。从现代和史前非洲人的不同群体中获得完整的基因组数据。随着这项技术的发展,未来的古代DNA研究有望
揭示更详细的非洲人类史前故事。人类的历史研究以前通过考古文字,基因技术的加入,可以把研究人类的历史推进到没有文字没有金属的远古时代。基因技术不仅研究未来,也研究过去。文章介绍了考古所用的ancient DNA 的技术发展。在非洲大陆上考古,各个地区,国家,部落,文明的研究与基因技术考古的运用。对基因考古人类文明感兴趣的朋友,推荐阅读该文章和文章的参考文献。
IF:3.700Q2
Current opinion in genetics & development,
2020-06.
DOI: 10.1016/j.gde.2020.05.008
PMID: 32563853
Abstract:
The history of human populations in Africa is complex and includes various demographic events that influenced patterns of genetic variation across the continent. Through genetic studies of modern-day, and most …
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The history of human populations in Africa is complex and includes various demographic events that influenced patterns of genetic variation across the continent. Through genetic studies of modern-day, and most recently, ancient African genetic variation, it became evident that deep African history is captured by the relationships among hunter-gatherers. Furthermore, it was shown that agriculture had a large influence on the distribution of current-day Africans. These later population movements changed the demographic face of the continent and descendants of farming groups today form the majority populations across Africa. Ancient DNA methods are continually evolving, and we see evidence of this in how research has advanced in the last decade. With the increased availability of full genomic data from diverse sets of modern-day and prehistoric Africans we now have more power to infer human demography. Future ancient DNA research promises to reveal more detailed stories of human prehistory in Africa.
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744.
小擎子
(2022-10-31 23:59):
#paper doi:10.1126/science.aao3290 Science, 2019, The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. 共生微生物组与转移性黑色素瘤患者的抗PD-1疗效相关,对免疫治疗有反应为R组,无反应为NR组。 文章开始用了16S测序、宏基因组测序和定量PCR,后比较发现,宏基因组的数据在R与NR的差异代表物种较少且与16S重叠(比较奇怪),后选用16S测序来做分析。在R组中,细菌物种, Bifidobacterium longum(长双歧杆菌), Collinsella aerofaciens(科林塞拉菌)和 Enterococcus faecium(屎肠球菌)含量较高,通过无菌小鼠实验,确认来自R组的粪便可以改善肿瘤控制,增强T细胞反应,提供抗PD-L1治疗的疗效。文献结尾的话,“除了微生物组之外,其他肿瘤和宿主因素会影响抗肿瘤免疫和癌症免疫治疗的疗效。Wnt/β-连环蛋白通路的肿瘤内在激活和Pte的缺失或突变已被证明会导致 T细胞浸润不足进入肿瘤微环境和对检查点阻断免疫疗法的耐药性。免疫调节基因中的种系多态性也有可能影响自发抗肿瘤T细胞反应的程度。我们在这里描述的结果开辟了将共生微生物组成以及肿瘤基因组学和种系遗传学整合到多参数模型中的途径,该模型可以最大限度地提高预测哪些患者可能对抗PD-1等免疫疗法产生反应的能力。”
Abstract:
Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition …
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Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients' microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16 ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included , , and Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti-PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.
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745.
沈么是快乐星球
(2022-10-31 23:36):
#paper doi/abs/10.1111/nph.16552
1)Genome sequencing and assembly of L. japonica. 金银花基因组测序和组装。
2)Genome annotation and whole-genome duplication. 基因组注释与全基因组复制。系统发育分析,发现金银花与菊花、莴苣的亲缘关系最为密切,与菊花分化时间为87Ma。
3)Carotenoid accumulation at different stages of flower development. 花发育不同阶段类胡萝卜素的积累。类胡萝卜素浓度随着花的成熟而先降低后急剧增加,UPLC检测发现:叶黄素和β-胡萝卜素是不同花发育阶段的两种主要化合物。
4)Evolution and expression analysis of carotenogenesis genes. 胡萝卜素基因的进化和表达分析。PSY基因在金银花中扩张成一个小的基因家族,LjPSY1和LjPSY3同源基因可能是金银花WGD事件的产物。
5)Evolution and functional identification of carotenoid cleavage dioxygenases in flower coloration. 花着色中类胡萝卜素裂解双加氧酶(CCD)的进化和功能鉴定。全基因组的分析鉴定出7个CCD基因,5个亚家族,其中LjCCD4 和 LjCCD1b表达量比较高。体外酶活测定发现LjCCD4 和 LjCCD1b表达蛋白可将β-胡萝卜素、叶黄素和100-apo-β-胡萝卜素转化为无色和挥发性物质导致颜色发生变化。
Abstract:
Lonicera japonica is a widespread member of the Caprifoliaceae (honeysuckle) family utilized in traditional medical practices. This twining vine honeysuckle also is a much-sought ornamental, in part due to its …
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Lonicera japonica is a widespread member of the Caprifoliaceae (honeysuckle) family utilized in traditional medical practices. This twining vine honeysuckle also is a much-sought ornamental, in part due to its dynamic flower coloration, which changes from white to gold during development. The molecular mechanism underlying dynamic flower coloration in L. japonica was elucidated by integrating whole genome sequencing, transcriptomic analysis and biochemical assays. Here, we report a chromosome-level genome assembly of L. japonica, comprising nine pseudochromosomes with a total size of 843.2 Mb. We also provide evidence for a whole-genome duplication event in the lineage leading to L. japonica, which occurred after its divergence from Dipsacales and Asterales. Moreover, gene expression analysis not only revealed correlated expression of the relevant biosynthetic genes with carotenoid accumulation, but also suggested a role for carotenoid degradation in L. japonica's dynamic flower coloration. The variation of flower color is consistent with not only the observed carotenoid accumulation pattern, but also with the release of volatile apocarotenoids that presumably serve as pollinator attractants. Beyond novel insights into the evolution and dynamics of flower coloration, the high-quality L. japonica genome sequence also provides a foundation for molecular breeding to improve desired characteristics.
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746.
林李泽强
(2022-10-31 23:29):
#paper doi:arxiv.org/abs/2210.09217 Statistical learning methods for neuroimaging data analysis with applications
这是一篇尚未发布得预印本,作者是具有统计学背景的研究人员。
在这篇文章中,作者从统计学的角度全面回顾了从神经成像技术到大规模神经成像研究再到统计学习方法中的统计问题。
文中有三个主要的内容:(1)从统计学视角看待和综述影像处理方法;(2)介绍了当前最前沿的几个神经成像数据集;(3)从统计学视角介绍了9类影像数据的统计方法。
这篇文章从统计学的角度讲述神经成像领域的问题,适合具有数理背景的作为领域入门读物,当然也适合其他背景的研究人员站在统计学角度看待神经成像数据分析中的问题。
arXiv,
2022.
Abstract:
The aim of this paper is to provide a comprehensive review of statistical challenges in neuroimaging data analysis from neuroimaging techniques to large-scale neuroimaging studies to statistical learning methods. We …
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The aim of this paper is to provide a comprehensive review of statistical challenges in neuroimaging data analysis from neuroimaging techniques to large-scale neuroimaging studies to statistical learning methods. We briefly review eight popular neuroimaging techniques and their potential applications in neuroscience research and clinical translation. We delineate the four common themes of neuroimaging data and review major image processing analysis methods for processing neuroimaging data at the individual level. We briefly review four large-scale neuroimaging-related studies and a consortium on imaging genomics and discuss four common themes of neuroimaging data analysis at the population level. We review nine major population-based statistical analysis methods and their associated statistical challenges and present recent progress in statistical methodology to address these challenges.
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747.
Arwen
(2022-10-31 23:28):
#paper https://doi.org/10.1016/j.neuroimage.2021.118799 Longitudinal brain atlases of early developing cynomolgus macaques from birth to 48 months of age 具有密集采样时间点和解剖信息的纵向脑图谱对研究人类和非人类灵长类动物婴儿期大脑的早期发育特征具有重要意义。然而,对于非人类灵长类动物这种对于理解人类大脑有极大帮助的动物模型来说,现有的大脑图谱主要是基于成人或青少年的,明显能够覆盖早期脑发育阶段的密集脑图谱。为填补这一空白,作者团队基于39只食蟹猴的175个纵向MRI数据,构建了一套纵向的脑图谱和组织分割概率图,共包含从出生到4岁(即1、2、3、4、5、6、9、12、18、24、36和48月龄)的12个时间点。
Abstract:
Longitudinal brain imaging atlases with densely sampled time-points and ancillary anatomical information are of fundamental importance in studying early developmental characteristics of human and non-human primate brains during infancy, which …
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Longitudinal brain imaging atlases with densely sampled time-points and ancillary anatomical information are of fundamental importance in studying early developmental characteristics of human and non-human primate brains during infancy, which feature extremely dynamic imaging appearance, brain shape and size. However, for non-human primates, which are highly valuable animal models for understanding human brains, the existing brain atlases are mainly developed based on adults or adolescents, denoting a notable lack of temporally densely-sampled atlases covering the dynamic early brain development. To fill this critical gap, in this paper, we construct a comprehensive set of longitudinal brain atlases and associated tissue probability maps (gray matter, white matter, and cerebrospinal fluid) with totally 12 time-points from birth to 4 years of age (i.e., 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 months of age) based on 175 longitudinal structural MRI scans from 39 typically-developing cynomolgus macaques, by leveraging state-of-the-art computational techniques tailored for early developing brains. Furthermore, to facilitate region-based analysis using our atlases, we also provide two popular hierarchy parcellations, i.e., cortical hierarchy maps (6 levels) and subcortical hierarchy maps (6 levels), on our longitudinal macaque brain atlases. These early developing atlases, which have the densest time-points during infancy (to the best of our knowledge), will greatly facilitate the studies of macaque brain development.
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748.
LXJ
(2022-10-31 23:26):
#paper DOI:10.1158/2159-8290.CD-21-1059 Hallmarks of Cancer: New Dimensions 癌症概念化的特征是一种启发式工具,将超级复杂的癌症表型与基因型提炼为一组现行但 未来可能出现变动的基本定律。随着人们对癌症发生发展机制的认知逐步完善,该疾病的其他方面已成为潜在的(认知)优化(方向)。本文对未来癌症研究的展望是:表型可塑性和分化中断是一种彼此不相关的标志性能力,并且非突变表观遗传重编程和多态微生物组是促进(癌症)获得标志性能力的独特有利特征。此外,不同来源的衰老细胞可能会被添加到肿瘤微环境重要功能细胞名单中。(最近半个月在读的文献, 肿瘤研究领域非常经典的文献第三版,Hanahan今年1月份发表在Cancer Discov,遇到困扰时就翻出来看一下)
Abstract:
The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer …
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The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment. SIGNIFICANCE: Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.
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749.
muton
(2022-10-31 23:23):
#paper https://doi.org/10.1523/JNEUROSCI.1449-20.2020 FFA and OFA Encode Distinct Types of Face Identity Information 在人的大脑中有诸多加工人脸的脑区,然而,这些加工人脸的脑区各自负责加工人脸当中的什么信息呢?作者基于此点思考,对三个面孔识别区(FFA梭状回、OFA枕叶面孔加工区和pSTS颞上沟)观看不同人脸得到的fMRI数据使用表征相似性分析的方法进行分析,比较了每个脑区的表征距离和代表身份信息模型的差异,结果发现FFA和OFA所代表的信息存在显著差异。FFA中人脸身份之间的差异是由感知相似性,社会特征,性别和OpenFace网络的差异引起的。相比之下,OFA中的表征距离主要是由低级的基于图像属性的差异(像素级和Gabor-Jet差异)驱动的。也就是说,尽管FFA和OFA都可以区分身份,但FFA相比于OFA,编码更高层次的感知和社会面孔的信息。
Abstract:
Faces of different people elicit distinct fMRI patterns in several face-selective regions of the human brain. Here we used representational similarity analysis to investigate what type of identity-distinguishing information is …
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Faces of different people elicit distinct fMRI patterns in several face-selective regions of the human brain. Here we used representational similarity analysis to investigate what type of identity-distinguishing information is encoded in three face-selective regions: fusiform face area (FFA), occipital face area (OFA), and posterior superior temporal sulcus (pSTS). In a sample of 30 human participants (22 females, 8 males), we used fMRI to measure brain activity patterns elicited by naturalistic videos of famous face identities, and compared their representational distances in each region with models of the differences between identities. We built diverse candidate models, ranging from low-level image-computable properties (pixel-wise, GIST, and Gabor-Jet dissimilarities), through higher-level image-computable descriptions (OpenFace deep neural network, trained to cluster faces by identity), to complex human-rated properties (perceived similarity, social traits, and gender). We found marked differences in the information represented by the FFA and OFA. Dissimilarities between face identities in FFA were accounted for by differences in perceived similarity, Social Traits, Gender, and by the OpenFace network. In contrast, representational distances in OFA were mainly driven by differences in low-level image-based properties (pixel-wise and Gabor-Jet dissimilarities). Our results suggest that, although FFA and OFA can both discriminate between identities, the FFA representation is further removed from the image, encoding higher-level perceptual and social face information. Recent studies using fMRI have shown that several face-responsive brain regions can distinguish between different face identities. It is however unclear whether these different face-responsive regions distinguish between identities in similar or different ways. We used representational similarity analysis to investigate the computations within three brain regions in response to naturalistically varying videos of face identities. Our results revealed that two regions, the fusiform face area and the occipital face area, encode distinct identity information about faces. Although identity can be decoded from both regions, identity representations in fusiform face area primarily contained information about social traits, gender, and high-level visual features, whereas occipital face area primarily represented lower-level image features.
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750.
张贝
(2022-10-31 23:21):
#paper Nat Med. 2022 Apr;28(4):704-712.
doi: 10.1038/s41591-022-01694-6.Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial.本文介绍了一项开放标签单中心研究的临床I期实验结果,在纳入的30例患者中(中位年龄为66岁,72%的患者为男性),以2:1的比例随机分组,分别接受CBM588+纳武利尤-伊匹单抗联合治疗以及仅使用纳武利尤-伊匹单抗治疗。结果表明在转移性肾细胞癌患者中补充双歧因子活菌产品CBM588可增强免疫检查点抑制剂纳武利尤-伊匹单抗的治疗效果,显著延长肾细胞癌患者的无进展生存期(12.7个月vs2.5个月),说明肠道微生物影响转移性肾细胞癌的免疫治疗疗效。
Abstract:
Previous studies have suggested that the gut microbiome influences the response to checkpoint inhibitors (CPIs) in patients with cancer. CBM588 is a bifidogenic live bacterial product that we postulated could …
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Previous studies have suggested that the gut microbiome influences the response to checkpoint inhibitors (CPIs) in patients with cancer. CBM588 is a bifidogenic live bacterial product that we postulated could augment CPI response through modulation of the gut microbiome. In this open-label, single-center study (NCT03829111), 30 treatment-naive patients with metastatic renal cell carcinoma with clear cell and/or sarcomatoid histology and intermediate- or poor-risk disease were randomized 2:1 to receive nivolumab and ipilimumab with or without daily oral CBM588, respectively. Stool metagenomic sequencing was performed at multiple timepoints. The primary endpoint to compare the relative abundance of Bifidobacterium spp. at baseline and at 12 weeks was not met, and no significant differences in Bifidobacterium spp. or Shannon index associated with the addition of CBM588 to nivolumab-ipilimumab were detected. Secondary endpoints included response rate, progression-free survival (PFS) and toxicity. PFS was significantly longer in patients receiving nivolumab-ipilimumab with CBM588 than without (12.7 months versus 2.5 months, hazard ratio 0.15, 95% confidence interval 0.05-0.47, P = 0.001). Although not statistically significant, the response rate was also higher in patients receiving CBM588 (58% versus 20%, P = 0.06). No significant difference in toxicity was observed between the study arms. The data suggest that CBM588 appears to enhance the clinical outcome in patients with metastatic renal cell carcinoma treated with nivolumab-ipilimumab. Larger studies are warranted to confirm this clinical observation and elucidate the mechanism of action and the effects on microbiome and immune compartments.
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751.
Ricardo
(2022-10-31 23:13):
#paper doi:https://doi.org/10.1101/251512 Unbiased construction of a temporally consistent
morphological atlas of neonatal brain development 这是UCL一名已毕业的博士在博士期间做的新生儿脑模板构建的工作,但是一直没有见刊,至今还挂在bioRxiv上。为构建无偏的脑模板,作者首先通过成对的线性配准寻找公共空间,在这个全局配准阶段,模板构建算法可以暂时忽略全局的形状变化,而专注于局部的形变。其次,作者介绍了一个快速且无偏的配准算法。最后,作者利用kernel regression的方法分配每个被试的权重,用于生成对应孕周的脑模板。
bioRxiv,
2018.
DOI: 10.1101/251512
Abstract:
AbstractPremature birth increases the risk of developing neurocognitive and neurobe-havioural disorders. The mechanisms of altered brain development causing these disorders are yet unknown. Studying the morphology and function of the …
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AbstractPremature birth increases the risk of developing neurocognitive and neurobe-havioural disorders. The mechanisms of altered brain development causing these disorders are yet unknown. Studying the morphology and function of the brain during maturation provides us not only with a better understanding of normal development, but may help us to identify causes of abnormal development and their consequences. A particular difficulty is to distinguish abnormal patterns of neurodevelopment from normal variation. The Developing Human Connectome Project (dHCP) seeks to create a detailed four-dimensional (4D) connectome of early life. This connectome may provide insights into normal as well as abnormal patterns of brain development. As part of this project, more than a thousand healthy fetal and neonatal brains will be scanned in vivo. This requires computational methods which scale well to larger data sets. We propose a novel groupwise method for the construction of a spatio-temporal model of mean morphology from cross-sectional brain scans at different gestational ages. This model scales linearly with the number of images and thus improves upon methods used to build existing public neonatal atlases, which derive correspondence between all pairs of images. By jointly estimating mean shape and longitudinal change, the atlas created with our method overcomes temporal inconsistencies, which are encountered when mean shape and intensity images are constructed separately for each time point. Using this approach, we have constructed a spatio-temporal atlas from 275 healthy neonates between 35 and 44 weeks post-menstrual age (PMA). The resulting atlas qualitatively preserves cortical details significantly better than publicly available atlases. This is moreover confirmed by a number of quantitative measures of the quality of the spatial normalisation and sharpness of the resulting template brain images.
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752.
魏魏魏
(2022-10-31 22:51):
#paper doi:10.1111/cdev.13002 Child Development, (2017), Adolescent Perceptions of Parental Privacy Invasion and Adolescent Secrecy: An Illustration of Simpson’s Paradox. 该研究探讨了父母对子女隐私的侵犯与青少年子女隐私之间的关系,这属于亲子关系的深入探讨,而且是对青少年群体的研究。青少年的隐私与被视为隐私侵犯的父母行为之间的关系是复杂的,该研究试图通过交叉滞后研究探讨两个变量之间的因果关系。在当前研究中,青少年前后三次报告了感知到的父母隐私侵犯行为和隐私的情况。结果发现,隐私侵犯行为正向预测子女的保密行为,这一关系反过来也是成立的。控制了正向的群体水平上的相关这个混淆变量的影响后,个体水平上的相关呈现出负相关关系。再个体水平上,较高保密行为预测了较低的隐私侵犯行为。这一结果与人们的常识或朴素的感觉是冲突的,因此,相关研究应该深入进行。
Abstract:
Adolescents' secrecy is intertwined with perception of parents' behaviors as acts of privacy invasion. It is currently untested, however, how this transactional process operates at the within-person level-where these causal …
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Adolescents' secrecy is intertwined with perception of parents' behaviors as acts of privacy invasion. It is currently untested, however, how this transactional process operates at the within-person level-where these causal processes take place. Dutch adolescents (n = 244, M = 13.84, 38.50% boys) reported three times on perceived parental privacy invasion and secrecy. Cross-lagged panel models (CLPM) confirmed earlier findings. Privacy invasion predicted increased secrecy, but a reverse effect was found from increased secrecy to increased privacy invasion. Controlling for confounding positive group-level associations with a novel random intercept CLPM, negative within-person associations were found. Higher levels of secrecy predicted lower levels of privacy invasive behaviors at the within-person level. These opposing findings within- versus between-persons illustrate a Simpson's paradox.
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753.
小W
(2022-10-31 22:14):
#paper doi:https://doi.org/10.1038/s42255-022-00636-3 Metabolic collateral lethal target identification reveals MTHFD2 paralogue dependency in ovarian cancer 基因组结构改变导致肿瘤抑制基因功能缺失失活,是肿瘤发生的重要驱动因素。这些缺失为癌细胞提供了功能和适应性优势,但由于邻近染色体中的必要基因的缺失,为了避免癌细胞死亡,这些细胞会找到一种具有类似功能的基因以保持细胞存活。本文作者设计了一个集成的工作流程(CLIM),利用癌症患者(TCGA)的基因组和转录组学特征来识别代谢基因缺失,重建基因组规模代谢模型(GSMMs),进行基于细胞目标的代谢通量分析,来揭示副致死靶向的代偿代谢途径。通过抑制副致死靶向的代偿代谢途径,达到精准杀死肿瘤细胞的目的。通过该算法,该团队成功在高级别浆液性卵巢癌(HGSOC)中 预测出 伴随 19p13.3 缺失 的代谢基因 UQCR11 及其 旁系途径 MTHFD2。实验部分通过示踪剂动态追踪实验、UQCR11/MTHFD2 缺失细胞代谢变化、 MTHFD2 基因是否敲除 的19p13.3 肿瘤小鼠模型的肿瘤生长等实验验证了预测的副致死靶点的有效性。
Abstract:
Recurrent loss-of-function deletions cause frequent inactivation of tumour suppressor genes but often also involve the collateral deletion of essential genes in chromosomal proximity, engendering dependence on paralogues that maintain similar …
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Recurrent loss-of-function deletions cause frequent inactivation of tumour suppressor genes but often also involve the collateral deletion of essential genes in chromosomal proximity, engendering dependence on paralogues that maintain similar function. Although these paralogues are attractive anticancer targets, no methodology exists to uncover such collateral lethal genes. Here we report a framework for collateral lethal gene identification via metabolic fluxes, CLIM, and use it to reveal MTHFD2 as a collateral lethal gene in UQCR11-deleted ovarian tumours. We show that MTHFD2 has a non-canonical oxidative function to provide mitochondrial NAD, and demonstrate the regulation of systemic metabolic activity by the paralogue metabolic pathway maintaining metabolic flux compensation. This UQCR11-MTHFD2 collateral lethality is confirmed in vivo, with MTHFD2 inhibition leading to complete remission of UQCR11-deleted ovarian tumours. Using CLIM's machine learning and genome-scale metabolic flux analysis, we elucidate the broad efficacy of targeting MTHFD2 despite distinct cancer genetic profiles co-occurring with UQCR11 deletion and irrespective of stromal compositions of tumours.
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754.
cellsarts
(2022-10-31 22:09):
#PaperDOI: 10.2217/fmb.12.61阴沟肠杆菌复合体:临床影响和新出现的抗生素耐药性Enterobacter cloacae complex: Clinical impact and emerging antibiotic resistance
July 2012Future Microbiology 7(7):887-902阴沟肠杆菌复合体的种类在自然界中广泛存在,但它们可以作为病原体。阴沟肠杆菌的生物化学和分子研究显示出基因组的异质性,包括 Enterobacter cloacae/ 阴沟肠杆菌 , Enterobacter asburiae/ 阿斯帛肠杆菌 , Enterobacter hormaechei/霍马埃希肠杆菌, Enterobacter kobei/ 哥贝肠杆菌, Enterobacter ludwigii/路德维希肠杆菌、 and Enterobacter nimipressuralis/ 米克雷肠杆菌 肠杆菌6种,其中阴沟肠杆菌和霍马埃希肠杆菌是人类临床标本中分离最频繁的两种。对属于这个分类单元的所有物种进行表型鉴定通常是困难的,而且并不总是可靠的;因此,分子生物学方法经常被使用。尽管阴沟肠杆菌复合菌株是过去十年中最常见的引起医院血流感染的肠杆菌属,但对其毒性相关特性知之甚少。相比之下,关于这些微生物的耐药特征已经发表了很多文章。事实上,它们能够通过对染色体基因的去抑制或在质粒上获得可转移的AmpC基因而产生过量的AmpC β-内酰胺酶。最近获得了许多其他的耐药决定因素,这些决定因素可以使几乎所有抗生素家族失效。对阴沟肠杆菌、霍氏肠杆菌和阿氏肠杆菌的药敏研究较多;这些研究报告了物种之间的微小差异,唯一显著的差异没有区分特征。
Abstract:
Species of the Enterobacter cloacae complex are widely encountered in nature, but they can act as pathogens. The biochemical and molecular studies on E. cloacae have shown genomic heterogeneity, comprising …
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Species of the Enterobacter cloacae complex are widely encountered in nature, but they can act as pathogens. The biochemical and molecular studies on E. cloacae have shown genomic heterogeneity, comprising six species: Enterobacter cloacae, Enterobacter asburiae, Enterobacter hormaechei, Enterobacter kobei, Enterobacter ludwigii and Enterobacter nimipressuralis, E. cloacae and E. hormaechei are the most frequently isolated in human clinical specimens. Phenotypic identification of all species belonging to this taxon is usually difficult and not always reliable; therefore, molecular methods are often used. Although the E. cloacae complex strains are among the most common Enterobacter spp. causing nosocomial bloodstream infections in the last decade, little is known about their virulence-associated properties. By contrast, much has been published on the antibiotic-resistance features of these microorganisms. In fact, they are capable of overproducing AmpC β-lactamases by derepression of a chromosomal gene or by the acquisition of a transferable ampC gene on plasmids conferring the antibiotic resistance. Many other resistance determinants that are able to render ineffective almost all antibiotic families have been recently acquired. Most studies on antimicrobial susceptibility are focused on E. cloacae, E. hormaechei and E. asburiae; these studies reported small variations between the species, and the only significant differences had no discriminating features.
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755.
小年
(2022-10-31 21:19):
#paper doi:10.1016/j.gpb.2022.09.004. ncFO: A Comprehensive Resource of Curated and Predicted ncRNAs Associated with Ferroptosis. Genomics Proteomics Bioinformatics. 2022.
细胞死亡在组织发育和体内平衡中起关键作用,并抑制癌细胞的过度增殖。铁死亡是由脂质过氧化诱导的一种特殊类型的调节性细胞死亡方式,探索铁死亡的潜在调节因子将有助于阐明其分子机制和仔细研究潜在的药物靶点。
目前虽然有铁死亡与疾病关联的调节剂和标志物数据库FerrD,但不便于研究人员对铁死亡相关非编码RNA(ncRNA,包括miRNA、lncRNA、circRNA)进行系统研究,ncRNA已被证实参与铁死亡的调节,文献中的信息不方便研究人员从综合角度表征铁死亡相关的ncRNA。为了填补这一空白,作者开发了ncRNA-铁死亡关联数据库(ncFO, http://www.jianglab.cn/ncFO/),ncFO是第一个收集了实验验证的铁死亡相关ncRNA并预测候选ncRNA-铁死亡关联的平台。用户可以获得经过实验验证的ncRNA-铁死亡关联,包括ncRNA名称、疾病、物种、组织、靶标、调控、发表时间和PMID。此外,ncFO数据库还提供了ncRNA的生存分析和差异表达分析。数据库为查询和分析铁死亡相关的ncRNA提供可靠的分析平台,为癌症治疗靶点的识别提供参考。
Abstract:
Ferroptosis is a form of regulated cell death driven by the accumulation of lipid hydroperoxides. Regulation of ferroptosis might be beneficial to cancer treatment. Non-coding RNAs (ncRNAs) are a class …
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Ferroptosis is a form of regulated cell death driven by the accumulation of lipid hydroperoxides. Regulation of ferroptosis might be beneficial to cancer treatment. Non-coding RNAs (ncRNAs) are a class of RNA transcripts that generally cannot encode proteins and have been demonstrated to play critical roles in regulating ferroptosis. Herein, we developed ncFO, the ncRNA-ferroptosis association database, to document the manually curated and predicted ncRNAs that are associated with ferroptosis. Collectively, ncFO contains 90 experimentally verified entries, including 46 microRNAs (miRNAs), 21 long non-coding RNAs (lncRNAs), and 17 circular RNAs (circRNAs). In addition, ncFO also incorporates two online prediction tools based on the regulation and co-expression of ncRNA and ferroptosis genes. Using default parameters, we obtained 3260 predicted entries, including 598 miRNAs and 178 lncRNAs, by regulation, as well as 2,592,661 predicted entries, including 967 miRNAs and 9632 lncRNAs, by ncRNA-ferroptosis gene co-expression in more than 8000 samples across 20 cancer types. The detailed information of each entry includes ncRNA name, disease, species, tissue, target, regulation, publication time, and PubMed identifier. ncFO also provides survival analysis and differential expression analysis for ncRNAs. In summary, ncFO offers a user-friendly platform to search and predict ferroptosis-associated ncRNAs, which might facilitate research on ferroptosis and discover potential targets for cancer treatment. ncFO can be accessed at http://www.jianglab.cn/ncFO/.
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756.
半面阳光
(2022-10-31 19:53):
#paper DOI: 10.1038/s41436-019-0686-8, 2019, Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). 这篇文献是ACMG和ClinGen发布的关于临床上拷贝数变异(CNVs)检测结果解读的指南。过去十几年中染色体芯片chromosomal microarray(CMA)技术已被广泛用于拷贝数变异检测,近年来基于二代测序(NGS)的CNV-Seq技术也被越来越广泛地应用于临床染色体拷贝数变异检测中。大部分检出的CNVs是独特的,需要进一步对其致病性进行评估。准确地进行临床CNVs致病性解读至关重要,并且需要一个标准化的解读方法和流程,来确保不同实验室之间解读的一致性。这篇指南首先确定了可用于对CNVs进行分类的证据类型,包括:基因组成分、剂量敏感性预测和梳理、预测功能效应、与临床文献报道病例的重叠与否、病例与对照数据库证据、以及个体CNVs的遗传模式。接着对这些不同类型的证据分配的不同的权重,最后形成了一个半定量的计分系统。这篇指南对这个评分系统的形成过程、各个记分点的说明、记分系统的使用、以及应用举例进行了详细的阐释。这一指南是目前国内外进行CNVs解读的主要参考文献。读这篇文章的体会有二,一是信息量极大,需要反复详细阅读;二是需要配合案例实际操作,才能充分理解。
IF:6.600Q1
Genetics in medicine : official journal of the American College of Medical Genetics,
2020-02.
DOI: 10.1038/s41436-019-0686-8
PMID: 31690835
Abstract:
PURPOSE: Copy-number analysis to detect disease-causing losses and gains across the genome is recommended for the evaluation of individuals with neurodevelopmental disorders and/or multiple congenital anomalies, as well as for …
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PURPOSE: Copy-number analysis to detect disease-causing losses and gains across the genome is recommended for the evaluation of individuals with neurodevelopmental disorders and/or multiple congenital anomalies, as well as for fetuses with ultrasound abnormalities. In the decade that this analysis has been in widespread clinical use, tremendous strides have been made in understanding the effects of copy-number variants (CNVs) in both affected individuals and the general population. However, continued broad implementation of array and next-generation sequencing-based technologies will expand the types of CNVs encountered in the clinical setting, as well as our understanding of their impact on human health.METHODS: To assist clinical laboratories in the classification and reporting of CNVs, irrespective of the technology used to identify them, the American College of Medical Genetics and Genomics has developed the following professional standards in collaboration with the National Institutes of Health (NIH)-funded Clinical Genome Resource (ClinGen) project.RESULTS: This update introduces a quantitative, evidence-based scoring framework; encourages the implementation of the five-tier classification system widely used in sequence variant classification; and recommends "uncoupling" the evidence-based classification of a variant from its potential implications for a particular individual.CONCLUSION: These professional standards will guide the evaluation of constitutional CNVs and encourage consistency and transparency across clinical laboratories.
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757.
xh
(2022-10-31 18:25):
#paper Applying CRISPR/Cas for genome engineering in plants: the best is yet to come https://doi.org/10.1016/j.pbi.2016.11.011文章介绍了crispr/cas9的两种方法同源重组(HR)和非同源末端连接(NHEJ)
Abstract:
Less than 5 years ago the CRISPR/Cas nuclease was first introduced into eukaryotes, shortly becoming the most efficient and widely used tool for genome engineering. For plants, efforts were centred …
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Less than 5 years ago the CRISPR/Cas nuclease was first introduced into eukaryotes, shortly becoming the most efficient and widely used tool for genome engineering. For plants, efforts were centred on obtaining heritable changes in most transformable crop species by inducing mutations into open reading frames of interest, via non-homologous end joining. Now it is important to take the next steps and further develop the technology to reach its full potential. For breeding, besides using DNA-free editing and avoiding off target effects, it will be desirable to apply the system for the mutation of regulatory elements and for more complex genome rearrangements. Targeting enzymatic activities, like transcriptional regulators or DNA modifying enzymes, will be important for plant biology in the future.
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758.
na na na
(2022-10-31 18:03):
#paper Big data in basic and translational cancer research doi: 10.1038/s41568-022-00502-0. Epub 2022 Sep 5,https://www.nature.com/articles/s41568-022-00502-0;分享一篇肿瘤大数据综述文章;在肿瘤领域,其研究焦点通常是关注肿瘤相关的生物途径和基因的突变/表达特征等,并和临床相结合进行转化;近年来,随着高通量技术的突破,大规模癌症组学数据的快速积累,研究者们或基于研究课题方向,或基于组学信息,或基于课题组资源,整理和构建了多个公共数据库,从而更好的通过公共资源以支持更多研究者的工作。本文回顾了通过大数据来推进癌症研究和治疗的现状和未来的挑战,比较系统性的描述了肿瘤研究领域的组学类型,组学特征,常见的研究方式和常用的公共数据库等信息,内容比较多也很全面。
Abstract:
Historically, the primary focus of cancer research has been molecular and clinical studies of a few essential pathways and genes. Recent years have seen the rapid accumulation of large-scale cancer …
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Historically, the primary focus of cancer research has been molecular and clinical studies of a few essential pathways and genes. Recent years have seen the rapid accumulation of large-scale cancer omics data catalysed by breakthroughs in high-throughput technologies. This fast data growth has given rise to an evolving concept of 'big data' in cancer, whose analysis demands large computational resources and can potentially bring novel insights into essential questions. Indeed, the combination of big data, bioinformatics and artificial intelligence has led to notable advances in our basic understanding of cancer biology and to translational advancements. Further advances will require a concerted effort among data scientists, clinicians, biologists and policymakers. Here, we review the current state of the art and future challenges for harnessing big data to advance cancer research and treatment.
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759.
钟鸣
(2022-10-31 17:38):
#paper doi:10.1186/s12864-022-08678-3 BMC Genomics,2022,From a large-scale genomic analysis of insertion sequences to insights into their regulatory roles in prokaryotes
插入序列(IS)作为可转移的外源序列,经常插入在原核生物基因组中。IS的插入有何影响?本文通过大范围的比较基因组分析探究了这个问题。在8481个基因组中鉴定到612700个IS插入,除了对这些IS和基因组类别进行分类描述外,作者还重点分析了IS的插入位置的偏好以及对基因组功能上的影响,他们发现IS普遍插入在基因功能与转录调控和转运活性有关的基因两侧,从而影响宿主的表型。IS影响宿主表型已是屡见不鲜,本研究从更广阔的范围内印证了这点,加深了我们对IS的了解,期望以后看到本领域更多的了解和新发现。
Abstract:
BACKGROUND: Insertion sequences (ISs) are mobile repeat sequences and most of them can copy themselves to new host genome locations, leading to genome plasticity and gene regulation in prokaryotes. In …
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BACKGROUND: Insertion sequences (ISs) are mobile repeat sequences and most of them can copy themselves to new host genome locations, leading to genome plasticity and gene regulation in prokaryotes. In this study, we present functional and evolutionary relationships between IS and neighboring genes in a large-scale comparative genomic analysis.RESULTS: IS families were located in all prokaryotic phyla, with preferential occurrence of IS3, IS4, IS481, and IS5 families in Alpha-, Beta-, and Gammaproteobacteria, Actinobacteria and Firmicutes as well as in eukaryote host-associated organisms and autotrophic opportunistic pathogens. We defined the concept of the IS-Gene couple (IG), which allowed to highlight the functional and regulatory impacts of an IS on the closest gene. Genes involved in transcriptional regulation and transport activities were found overrepresented in IG. In particular, major facilitator superfamily (MFS) transporters, ATP-binding proteins and transposases raised as favorite neighboring gene functions of IS hotspots. Then, evolutionary conserved IS-Gene sets across taxonomic lineages enabled the classification of IS-gene couples into phylum, class-to-genus, and species syntenic IS-Gene couples. The IS5, IS21, IS4, IS607, IS91, ISL3 and IS200 families displayed two to four times more ISs in the phylum and/or class-to-genus syntenic IGs compared to other IS families. This indicates that those families were probably inserted earlier than others and then subjected to horizontal transfer, transposition and deletion events over time. In phylum syntenic IG category, Betaproteobacteria, Crenarchaeota, Calditrichae, Planctomycetes, Acidithiobacillia and Cyanobacteria phyla act as IS reservoirs for other phyla, and neighboring gene functions are mostly related to transcriptional regulators. Comparison of IS occurrences with predicted regulatory motifs led to ~ 26.5% of motif-containing ISs with 2 motifs per IS in average. These results, concomitantly with short IS-Gene distances, suggest that those ISs would interfere with the expression of neighboring genes and thus form strong candidates for an adaptive pairing.CONCLUSIONS: All together, our large-scale study provide new insights into the IS genetic context and strongly suggest their regulatory roles.
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760.
Vincent
(2022-10-31 15:22):
#paper Obtaining genetics insights from deep learning via explainable artificial intelligence, Nature Reviews Genetics https://doi.org/10.1038/ s41576-022-00532-2 基于深度学习的人工智能模型在基因组功能预测中发挥重要作用,被认为是当下表现最好的模型(state of the art)。但是由于深度学习模型的复杂性, 它们往往被认为是黑箱模型,其预测效果/机制往往很难被解释,但是基因组的研究中很多时候作用机制(过程)比预测效果(结果)更有价值。这篇review paper总结了近年来新兴的可解释性机器学习(xAI)技术在基因组领域的研究进展,展望了该技术在揭示生物机理方面的潜能。这篇文章主要以regulatory genomics 作为例子, 总结归纳了4种解释机器学习模型的技术:基于模型的解释(检查隐含层的神经元活动,注意力机制),影响的数学传播(前向传播/后向传播), 特征相互作用的鉴别,和基于先验知识的透明模型,以及这几种技术在高通量测序技术中的潜在假设和相应的局限性。
Abstract:
Artificial intelligence (AI) models based on deep learning now represent the state of the art for making functional predictions in genomics research. However, the underlying basis on which predictive models …
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Artificial intelligence (AI) models based on deep learning now represent the state of the art for making functional predictions in genomics research. However, the underlying basis on which predictive models make such predictions is often unknown. For genomics researchers, this missing explanatory information would frequently be of greater value than the predictions themselves, as it can enable new insights into genetic processes. We review progress in the emerging area of explainable AI (xAI), a field with the potential to empower life science researchers to gain mechanistic insights into complex deep learning models. We discuss and categorize approaches for model interpretation, including an intuitive understanding of how each approach works and their underlying assumptions and limitations in the context of typical high-throughput biological datasets.
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