上個月和預印本有關的最大新聞非nature的黃金開放獲取（golden open access）莫屬了【1】。該協議規定：如果作者希望以完全開放獲取形式發表文章，則需要支付11390美元（9500歐元）的開放獲取費（非強制）。開放獲取大潮來勢洶洶。關於開放獲取和其不同形式，我們曾在此前有過一篇推送介紹【2】，這裏只簡單說一下：科學出版是需要燒錢的，出版商又要賺錢，所以他們要想方設法拿到這筆錢。傳統上這筆錢由讀者支付（一般是學校或科研機構的圖書館訂購但只有訂購單位能看文章），而現今另一種流行方式就是由作者支付，所謂開放獲取（換言之作者出錢讓任何人都可以看自己的文章）。
然而，對nature集團的此舉，科學家們似乎頗不買賬，主要原因大概還是這個要價太離譜。與現今最成功、影響力最大、收費恐怕也最高的OA雜誌nature communication的5380美元相比，這個價格確實顯得比較高，不過一個理由可能是這次參與的33本雜誌影響力也許更大（囊括nature正刊和國內朋友說的大子刊）。當然，nature方面也給出了自己的說法，這裏不再贅述（詳見【1】）。
讓我們看看學者們的一些反應：
摘自【1】
多倫多大學生物信息學家Michael Hoffman發推嘲諷價格很low
西班牙科爾多巴大學微生物學教授Garcia-Fernandez表示：猜測（如此高昂的OA費）將會被nature集團用以向審稿人支付佣金了吧……這不是science，這就是business。
10月初，德國著名科研機構馬克思普朗克研究所（max plank institute）剛剛同Springer Nature出版集團達成協議，“該協議允許參與機構的作者在 Nature 及其 33 種系列期刊上免費發表開放獲取（OA）文章，參與機構還可以獲得對 Nature 系列期刊的閱讀權限，包括 Nature Review 系列期刊和所有即將推出的 Nature 品牌刊“【1】。該協議將於21年1月生效，爲期四年。對此，曾接受過我們生信人專訪的新興論文發表（準確地說是預印本文章推薦）平臺PCI（https://peercommunityin.org/）也發推，內容很簡單：
在此，小編向大家建議，試試biorxiv + PCI吧！這裏有完全免費的平臺（biorixv），以及高水平科學家的審稿被接受後即可獲得doi和引用，日益增長的認可度，理論上可取得與常規高水平雜誌上發表文章類似的效果，且此後還可以繼續向其他雜誌投稿（PCI）【3】。
每月月底，小編都會有些頭疼，因爲在每月大量的biorxiv預印本中選出小編眼中十篇所謂的“生信好文”實在不是一件容易的事，且疏漏難免。從本期開始，我們會通過“查缺補漏”的方式爲大家呈遞這些在當月被忽略的文章。第一篇“補漏”的文章，來自巴黎薩克雷大學（Université Paris-Saclay）的研究團隊領導的一項研究，科學家們對Tara Oceans項目中的宏基因組數據進行分析，完成了其中700個真核生物微生物組的分箱，可以說極大擴充了我們對於海洋原生生物的認識。與此同時，我們也在副推中爲大家帶來這一全球著名的大洋科考項目的更多介紹。
1.【熱文】劍橋大學學者：細菌泛基因組單鹼基水平解析
Nucleotide-resolution bacterial pan-genomics with reference graphs
Bacterial genomes follow a U-shaped frequency distribution whereby most genomic loci are either rare (accessory) or common (core) - the alignable fraction of two genomes from a single species might be only 50%. Standard tools therefore analyse mutations only in the core genome, ignoring accessory mutations. We present a novel pan-genome graph structure and algorithms implemented in the software pandora, which approximates a sequenced genome as a recombinant of reference genomes, detects novel variation and then pan-genotypes multiple samples. Constructing a reference graph from 578 E. coli genomes, we analyse a diverse set of 20 E. coli isolates. We show, for rare variants, pandora recovers at least 13k more SNPs than single-reference based tools, achieving equal or better error rates with Nanopore as with Illumina data, and providing a stable framework for analysing diverse samples without reference bias. This is a significant step towards comprehensive analyses of bacterial genetic variation.
2.【樞紐】斯坦福大學Howard Chang：染色體外DNA 樞紐（EcDNA hubs）對原癌基因表達的重要作用
EcDNA hubs drive cooperative intermolecular oncogene expression
Extrachromosomal DNAs (ecDNAs) are prevalent in human cancers and mediate high oncogene expression through elevated copy number and altered gene regulation1. Gene expression typically involves distal enhancer DNA elements that contact and activate genes on the same chromosome2,3. Here we show that ecDNA hubs, comprised of ~10-100 ecDNAs clustered in the nucleus of interphase cells, drive intermolecular enhancer input for amplified oncogene expression. Single-molecule sequencing, single-cell multiome, and 3D enhancer connectome reveal subspecies of MYC-PVT1 ecDNAs lacking enhancers that access intermolecular and ectopic enhancer-promoter interactions in ecDNA hubs. ecDNA hubs persist without transcription and are tethered by BET protein BRD4. BET inhibitor JQ1 disperses ecDNA hubs, preferentially inhibits ecDNA oncogene transcription, and kills ecDNA+ cancer cells. Two amplified oncogenes MYC and FGFR2 intermix in ecDNA hubs, engage in intermolecular enhancer-promoter interactions, and transcription is uniformly sensitive to JQ1. Thus, ecDNA hubs are nuclear bodies of many ecDNAs tethered by proteins and platforms for cooperative transcription, leveraging the power of oncogene diversification and combinatorial DNA interactions. We suggest ecDNA hubs, rather than individual ecDNAs, as units of oncogene function, cooperative evolution, and new targets for cancer therapy.
(g) A schematic diagram of the proposed ecDNA hub 594model for intermolecular cooperation.
3.【尋根】範德堡大學（Vanderbilt University）Rokas組：追尋動物進化之“根”
Rooting the animal tree of life
There has been considerable debate about the placement of the root in the animal tree of life, which has emerged as one of the most challenging problems in animal phylogenetics. This debate has major implications for our understanding of the earliest events in animal evolution, including the origin of the nervous system. Some phylogenetic analyses support a root that places the first split in the phylogeny of living animals between sponges and all other animals (the Porifera-sister hypothesis), and others find support for a split between comb jellies and all other animals (Ctenophora-sister). These analyses differ in many respects, including in the genes considered, species considered, molecular evolution models, and software. Here we systematically explore the rooting of the animal tree of life under consistent conditions by synthesizing data and results from 15 previous phylogenomic studies and performing a comprehensive set of new standardized analyses. It has previously been suggested that site-heterogeneous models favor Porifera-sister, but we find that this is not the case. Rather, Porifera-sister is only obtained under a narrow set of conditions when the number of site-heterogeneous categories is unconstrained and range into the hundreds. Site-heterogenous models with a fixed number of dozens of categories support Ctenophora-sister, and cross-validation indicates that such models fit the data just as well as the unconstrained models. Our analyses shed light on an important source of variation between phylogenomic studies of the animal root. The datasets and analyses consolidated here will also be a useful test-platform for the development of phylogenomic methods for this and other difficult problems.
4.【表觀】加州大學洛杉磯分校（UCLA）Ernst組：1000個表觀基因組數據集對人類基因組的新註釋
Universal annotation of the human genome through integration of over a thousand epigenomic datasets
Genome-wide maps of chromatin marks such as histone modifications and open chromatin sites provide valuable information for annotating the non-coding genome, including identifying regulatory elements. Computational approaches such as ChromHMM have been applied to discover and annotate chromatin states defined by combinatorial and spatial patterns of chromatin marks within the same cell type. An alternative ‘stacked modeling’ approach was previously suggested, where chromatin states are defined jointly from datasets of multiple cell types to produce a single universal genome annotation based on all datasets. Despite its potential benefits for applications that are not specific to one cell type, such an approach was previously applied only for small-scale specialized purposes. Large-scale applications of stacked modeling have previously posed scalability challenges. In this paper, using a version of ChromHMM enhanced for large-scale applications, we applied the stacked modeling approach to produce a universal chromatin state annotation of the human genome using over 1000 datasets from more than 100 cell types, denoted the full-stack model. The full-stack model states show distinct enrichments for external genomic annotations, which we used in characterizing each state. Compared to cell-type-specific annotations, the full-stack annotation directly differentiates constitutive from cell-type-specific activity and is more predictive of locations of external genomic annotations. Overall, the full-stack ChromHMM model provides a universal chromatin state annotation of the genome and a unified global view of over 1000 datasets. We expect this to be a useful resource that complements existing cell-type-specific annotations for studying the non-coding human genome.
5.【搏命】東亞人祖先與類新冠病毒的一場“殊死搏殺”
An ancient coronavirus-like epidemic drove adaptation in East Asians from 25,000 to 5,000 years ago
The current SARS-CoV-2 pandemic has emphasized the vulnerability of human populations to novel viral pressures, despite the vast array of epidemiological and biomedical tools now available. Notably, modern human genomes contain evolutionary information tracing back tens of thousands of years, which may help identify the viruses that have impacted our ancestors – pointing to which viruses have future pandemic potential. Here, we apply evolutionary analyses to human genomic datasets to recover selection events involving tens of human genes that interact with coronaviruses, including SARS-CoV-2, that started 25,000 years ago. These adaptive events were limited to ancestral East Asian populations, the geographical origin of several modern coronavirus epidemics. An arms race with an ancient corona-like virus may thus have taken place in ancestral East Asian populations. By learning more about our ancient viral foes, our study highlights the promise of evolutionary information to combat the pandemics of the future.
6.【質譜】瑞士蘇黎世大學（University of Zurich）：使用R語言輕鬆對質譜原始數據進行操作
rawR - Direct access to raw mass spectrometry data in R
The Bioconductor project has shown that the R statistical environment is a highly valuable tool for genomics data analysis1, but with respect to proteomics we are still missing low level infrastructure to enable performant and robust analysis workflows in R. Fundamentally important are libraries that provide raw data access. Our R package rawDiag has provided the proof-of-principle how access to mass spectromerty raw files can be realized by wrapping vendor-provided APIs, but rather focused on meta data analysis and visualization2. Our novel package rawR now provides complete, OS independent access to all spectral data logged in Thermo Fisher Scientific raw files. In this technical note we present implementation details and describe the main functionality provided by the rawR package. In addition, we report two use cases inspired by real-word research task that demonstrate the application of the package.Availability https://github.com/fgcz/rawR
7.【G4】法國波爾多大學Gabelica組:一個DNA四鏈體結構的數據庫
DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions
G-quadruplex DNA structures have become attractive drug targets, and native mass spectrometry can provide detailed characterization of drug binding stoichiometry and affinity, potentially at high throughput. However, the G-quadruplex DNA polymorphism poses problems for interpreting ligand screening assays. In order to establish standardized MS-based screening assays, we studied 28 sequences with documented NMR structures in (usually 100 mM) K+, and report here their circular dichroism (CD), melting temperature (Tm), NMR spectra and electrospray mass spectra in 1 mM KCl/100 mM TMAA. Based on these results, we make a short-list of sequences that adopt the same structure in the MS assay as reported by NMR, and provide recommendations on using them for MS-based assays. We also built an R-based open-source application to build and consult a database, wherein further sequences can be incorporated in the future. The application handles automatically most of the data processing, and allows generating custom figures and reports. The database is included in the g4dbr package (https://github.com/EricLarG4/g4dbr) and can be explored online (https://ericlarg4.github.io/G4_database.html).
8.【新紀元】三代測序——宏基因組研究的新紀元？
Long read metagenomics, the next step?
Results Here we have used different 3rd generation techniques to study the metagenome of a well-known marine sample from the mixed epipelagic water column of the winter Mediterranean. We have compared Oxford Nanopore and PacBio last generation technologies with the classical approach using Illumina short reads followed by assembly. PacBio Sequel II CCS appears particularly suitable for cellular metagenomics due to its low error rate. Long reads allow efficient direct retrieval of complete genes (473M/Tb) and operons before assembly, facilitating annotation and compensates the limitations of short reads or short-read assemblies. MetaSPAdes was the most appropriate assembly program when used in combination with short reads. The assemblies of the long reads allow also the reconstruction of much more complete metagenome-assembled genomes, even from microbes with high microdiversity. The flexible genome of reconstructed MAGs is much more complete and allows rescuing more adaptive genes.
9.[天外]康奈爾大學:國際空間站中發現微生物的傳遞？
Genetic Evidence for Selective Transfer of Microbes Between the International Space Station and an Astronaut
Microbial transfer of both pathogenic and non-pathogenic strains from the environment can influence a person’s health, but such studies are rare and the phenomenon is difficult to study. Here, we use the unique, isolated environment of the International Space Station (ISS) to track environmental movement of microbes in an astronaut’s body. We identified several microbial taxa, including Serratia proteamaculans and Rickettsia australis, which appear to have been transferred from the environment of to the gut and oral microbiomes of the on-board astronaut, and also observed an exchange of genetic elements between the microbial species. Strains were matched at the SNP and haplotype-level, and notably some strains persisted even after the astronaut’s return to Earth. Finally, some transferred taxa correspond to secondary strains in the ISS environment, suggesting that this process may be mediated by evolutionary selection, and thus, continual microbial monitoring can be important to future spaceflight mission planning and habitat design.
10.【補漏】巴黎薩克雷大學Tom Delmont實驗室：世界最大海洋微生物組項目Tara Oceans裏挖掘到的真核生物宏基因組
Functional repertoire convergence of distantly related eukaryotic plankton lineages revealed by genome-resolved metagenomics
Marine planktonic eukaryotes play a critical role in global biogeochemical cycles and climate. However, their poor representation in culture collections limits our understanding of the evolutionary history and genomic underpinnings of planktonic ecosystems. Here, we used 280 billion metagenomic reads from 143 Tara Oceans stations to reconstruct and manually curate more than 700 abundant and widespread eukaryotic metagenome-assembled genomes ranging from 10 Mbp to up to 1.3 Gbp. The resulting non-redundant genomic resource of 25 billion nucleotides that describe 10 million genes covers a wide range of poorly characterized unicellular and multicellular eukaryotic lineages that complement the long-standing contributions of culture efforts to survey the tree of marine life while better representing plankton from the open ocean. Phylogeny of the DNA-dependent RNA polymerase placed this genomic resource in a comprehensive evolutionary framework that provided insights into the relationships of eukaryotic supergroups. From there, classification of unicellular eukaryotic plankton based on functions encoded in their genes revealed four major groups connecting distantly related lineages such as the diatoms and green algae. There has been a recurrent problem in understanding the interplay between eukaryotes’ vertical evolution and their phenotype. By disentangling phylogenetic signals from functional trends with genomics, we found that neither the classical trophic mode of plankton nor its vertical evolutionary history could fully explain the genomic functional landscape of marine eukaryotes that coexisted for millions of years.
引文
1.一篇文章7.4萬，Nature 33種期刊開放獲取新政引爭議，社區斥其寄生蟲（機器之心）
2.Montreal，起底開放獲取
3.Montreal：專訪PCI創始人:最低成本發Paper的初心與挑戰
原載於 生信人