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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 124,441 papers from 534,710 authors.

Most tweeted biology preprints, last 24 hours

*There are gaps in historical Twitter data, most notably in spring 2020. This may result in some preprints appearing with less tweets than they should.

234 results found. For more information, click each entry to expand.

1: SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome
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Posted 13 Dec 2020

SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome
108 tweets bioRxiv genomics

Liguo Zhang, Alexsia Richards, Andrew Khalil, Emile Wogram, Haiting Ma, Richard A. Young, Rudolf Jaenisch

Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests have been widely reported in patients after recovery, yet these patients most commonly are non-infectious. Here we investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome and that transcription of the integrated sequences might account for PCR-positive tests. In support of this hypothesis, we found chimeric transcripts consisting of viral fused to cellular sequences in published data sets of SARS-CoV-2 infected cultured cells and primary cells of patients, consistent with the transcription of viral sequences integrated into the genome. To experimentally corroborate the possibility of viral retro-integration, we describe evidence that SARS-CoV-2 RNAs can be reverse transcribed in human cells by reverse transcriptase (RT) from LINE-1 elements or by HIV-1 RT, and that these DNA sequences can be integrated into the cell genome and subsequently be transcribed. Human endogenous LINE-1 expression was induced upon SARS-CoV-2 infection or by cytokine exposure in cultured cells, suggesting a molecular mechanism for SARS-CoV-2 retro-integration in patients. This novel feature of SARS-CoV-2 infection may explain why patients can continue to produce viral RNA after recovery and suggests a new aspect of RNA virus replication.

2: Motility induced fracture reveals a ductile to brittle crossover in the epithelial tissues of a simple animal
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Posted 19 Jun 2019

Motility induced fracture reveals a ductile to brittle crossover in the epithelial tissues of a simple animal
37 tweets bioRxiv biophysics

Vivek N. Prakash, Matthew S. Bull, Manu Prakash

Animals are characterized by their movement, and their tissues are continuously subjected to dynamic force loading while they crawl, walk, run or swim [1]. Tissue mechanics fundamentally determine the ecological niches that can be endured by a living organism [2]. While epithelial tissues provide an important barrier function in animals, they are subjected to extreme strains during day to day physiological activities, such as breathing [1], feeding [3], and defense response [4]. However, failure or inability to withstand to these extreme strains can result in epithelial fractures [5, 6] and associated diseases [7,8]. From a materials science perspective, how properties of living cells and their interactions prescribe larger scale tissue rheology and adaptive response in dynamic force landscapes remains an important frontier [9]. Motivated by pushing tissues to the limits of their integrity, we carry out a multi-modal study of a simple yet highly dynamic organism, the Trichoplax Adhaerens [10,11,12], across four orders of magnitude in length (1um to 10 mm), and six orders in time (0.1 sec to 10 hours). We report the discovery of abrupt, bulk epithelial tissue fractures (10 sec) induced by the organisms own motility. Coupled with rapid healing (10 min), this discovery accounts for dramatic shape change and physiological asexual division in this early divergent metazoan. We generalize our understanding of this phenomena by codifying it in a heuristic model, highlighting the fundamental questions underlying the debonding/bonding criterion in a soft active living material by evoking the concept of an epithelial alloy. Using a suite of quantitative experimental and numerical techniques, we demonstrate a force driven ductile to brittle material transition governing the morphodynamics of tissues pushed to the edge of rupture. This work contributes to an important discussion at the core of developmental biology [13,14,15,16,17], with important applications to an emerging paradigm in materials and tissue engineering [5,18,19,20], wound healing and medicine [8,21,22].

3: In situ characterization of the 3D microanatomy of the pancreas and pancreatic cancer at single cell resolution
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Posted 09 Dec 2020

In situ characterization of the 3D microanatomy of the pancreas and pancreatic cancer at single cell resolution
37 tweets bioRxiv cancer biology

Ashley L. Kiemen, Alicia M. Braxton, Mia P. Grahn, Kyu S. Han, Jaanvi Mahesh Babu, Rebecca Reichel, Falone Amoa, Seung-Mo Hong, Toby C. Cornish, Elizabeth D Thompson, Laura D. Wood, Ralph H. Hruban, Pei-Hsun Wu, Denis Wirtz

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer. Accumulating evidence indicates the tumor microenvironment is highly associated with tumorigenesis through regulation of cellular physiology, signaling systems, and gene expression profiles of cancer cells. Yet the mechanisms by which the microenvironment evolves from normal pancreas architecture to precursor lesions and invasive cancer is poorly understood. Obtaining high-content and high-resolution information from a complex tumor microenvironment in large volumetric landscapes represents a key challenge in the field of cancer biology. To address this challenge, we established a novel method to reconstruct three-dimensional (3D) centimeter-scale tissues containing billions of cells from serially sectioned histological samples, utilizing deep learning approaches to recognize eight distinct tissue subtypes from hematoxylin and eosin stained sections at micrometer and single-cell resolution. Using samples from a range of normal, precancerous, and invasive pancreatic cancer tissue, we map in 3D modes of cancer invasion in the tumor microenvironment, and emphasize the need for further 3D quantification of biological systems.

4: Spatial structure impacts adaptive therapy by shaping intra-tumoral competition
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Posted 04 Nov 2020

Spatial structure impacts adaptive therapy by shaping intra-tumoral competition
25 tweets bioRxiv cancer biology

Maximilian A R Strobl, Jill Gallaher, Jeffrey West, Mark Robertson-Tessi, Philip K. Maini, Alexander Anderson

(1) Background: Adaptive therapy aims to tackle cancer drug resistance by leveraging intra-tumoral competition between drug-sensitive and resistant cells. Motivated by promising results in prostate cancer there is growing interest in extending this approach to other cancers. Here we present a theoretical study of intra-tumoral competition during adaptive therapy, to identify under which circumstances it will be superior to aggressive treatment; (2) Methods: We use a 2-D, on-lattice, agent-based tumour model to examine the impact of different microenvironmental factors on the comparison between continuous drug administration and adaptive therapy. (3) Results: We show that the degree of crowding, the initial resistance fraction, the presence of resistance costs, and the rate of tumour cell turnover are key determinants of the benefit of adaptive therapy, and we study in detail how these factors alter competition between cells. We find that intra-specific competition between resistant cells plays an unexpectedly important role in the ability to control resistance. To conclude we show how differences in resistance cost and turnover change the tumour's spatial organisation and may explain differences in cycling speed observed in a cohort of 67 prostate cancer patients undergoing intermittent androgen deprivation therapy; (4) Conclusion: Our work provides insights into how adaptive therapy leverages inter- and intra-specific competition to control resistance, and shows that the tumour's spatial architecture will likely be an important factor in determining the quantitative benefit of adaptive therapy in patients.

5: 3D Mapping of Neurofibrillary Tangle Burden in the Human Medial Temporal Lobe
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Posted 17 Jan 2021

3D Mapping of Neurofibrillary Tangle Burden in the Human Medial Temporal Lobe
18 tweets bioRxiv neuroscience

Paul A Yushkevich, Mónica Muñoz López, Maria Mercedes Iñiguez de Onzoño Martin, Ranjit Ittyerah, Sydney Lim, Sadhana Ravikumar, Madigan L. Bedard, Stephen Pickup, Weixia Liu, Jiancong Wang, Ling Yu Hung, Jade Lasserve, Nicolas Vergnet, Long Xie, Mengjin Dong, Salena Cui, Lauren McCollum, John L Robinson, Theresa Schuck, Robin de Flores, Murray Grossman, M. Dylan Tisdall, Karthik Prabhakaran, Gabor Mizsei, Sandhitsu R. Das, Emilio Artacho-Pérula, María del Mar Arroyo Jiménez, María Pilar Marcos Rabal, Francisco Javier Molina Romero, Sandra Cebada Sánchez, José Carlos Delgado González, Carlos de la Rosa-Prieto, Marta Córcoles Parada, Edward B. Lee, John Q Trojanowski, Daniel T. Ohm, Laura E.M. Wisse, David A. Wolk, David J. Irwin, Ricardo Insausti

Abstract Tau protein neurofibrillary tangles (NFT) are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease (AD) and related dementias. Our knowledge of the pattern of NFT progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in AD, is based on conventional 2D histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe (MTL) specimens were used to construct 3D quantitative maps of NFT burden in the MTL at individual and group levels. These maps reveal significant variation in NFT burden along the anterior-posterior axis. While early NFT pathology is thought to be confined to the transentorhinal region, we find similar levels of NFT burden in this region and other MTL subregions, including amygdala, temporopolar cortex, and subiculum/CA1.

6: Cognitive boundary signals in the human medial temporal lobe shape episodic memory representation
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Posted 16 Jan 2021

Cognitive boundary signals in the human medial temporal lobe shape episodic memory representation
17 tweets bioRxiv neuroscience

Jie Zheng, Andrea Gomez Palacio Schjetnan, Mar Yebra, Clayton P. Mosher, Suneil Kalia, Taufik A Valiante, Adam Mamelak, Gabriel Kreiman, Ueli Rutishauser

While experience unfolds continuously, memories are organized as a set of discrete events that bind together the "where", "when", and "what" of episodic memory. This segmentation of continuous experience is thought to be facilitated by the detection of salient environmental or cognitive events. However, the underlying neural mechanisms and how such segmentation shapes episodic memory representations remain unclear. We recorded from single neurons in the human medial temporal lobe while subjects watched videos with different types of embedded boundaries and were subsequently evaluated for memories of the video contents. Here we show neurons that signal the presence of cognitive boundaries between subevents from the same episode and neurons that detect the abstract separation between different episodes. The firing rate and spike timing of these boundary-responsive neurons were predictive of later memory retrieval accuracy. At the population level, abrupt neural state changes following boundaries predicted enhanced memory strength but impaired order memory, capturing the behavioral tradeoff subjects exhibited when recalling episodic content versus temporal order. Successful retrieval was associated with reinstatement of the neural state present following boundaries, indicating that boundaries structure memory search. These findings reveal a neuronal substrate for detecting cognitive boundaries and show that cognitive boundary signals facilitate the mnemonic organization of continuous experience as a set of discrete episodic events.

7: Anesthetics fragment hippocampal network activity, alter spine dynamics and affect memory consolidation
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Posted 06 Jun 2020

Anesthetics fragment hippocampal network activity, alter spine dynamics and affect memory consolidation
17 tweets bioRxiv neuroscience

Wei Yang, Mattia Chini, Jastyn A Poepplau, Andrey Formozov, Alexander Dieter, Patrick Piechocinski, Cynthia Rais, Fabio Morellini, Olaf Sporns, Ileana L Hanganu-Opatz, J. Simon Wiegert

General anesthesia is characterized by reversible loss of consciousness accompanied by transient amnesia. Yet, long-term memory impairment is an undesirable side-effect. How different types of general anesthetics (GAs) affect the hippocampus, a brain region central to memory formation and consolidation, is poorly understood. Using extracellular recordings, chronic 2-photon imaging and behavioral analysis, we monitor the effects of isoflurane (Iso), medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, and altered spine dynamics. CA1 network activity under all three anesthetics was different to natural sleep. Iso anesthesia most closely resembled unperturbed activity during wakefulness and sleep, and network alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory consolidation, with implications for GA strategy appraisal in animal research and clinical settings.

8: Recurrent mutations in SARS-CoV-2 genomes isolated from mink point to rapid host-adaptation
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Posted 16 Nov 2020

Recurrent mutations in SARS-CoV-2 genomes isolated from mink point to rapid host-adaptation
12 tweets bioRxiv genomics

Lucy van Dorp, Cedric CS Tan, Su Datt Lam, Damien Richard, Christopher Owen, Dorothea Berchtold, Christine Orengo, François Balloux

Severe acute respiratory coronavirus 2 (SARS-CoV-2), the agent of the ongoing COVID-19 pandemic, jumped into humans from an unknown animal reservoir in late 2019. In line with other coronaviruses, SARS-CoV-2 has the potential to infect a broad range of hosts. SARS-CoV-2 genomes have now been isolated from cats, dogs, lions, tigers and minks. SARS-CoV-2 seems to transmit particularly well in mink farms with outbreaks reported in Spain, Sweden, the Netherlands, Italy, the USA and Denmark. Genomic data from SARS-CoV-2 isolated from infected minks provides a natural case study of a secondary host jump of the virus, in this case from humans to animals, and occasionally back again. We screened published SARS-CoV-2 genomes isolated from minks for the presence of recurrent mutations common in mink but infrequent in SARS-CoV-2 genomes from human infections. We identify 23 recurrent mutations including three nonsynonymous mutations in the Receptor Binding Domain of the SARS-CoV-2 spike protein that independently emerged at least four times but are only very rarely observed in strains circulating in humans. The repeat emergence of mutations across phylogenetically distinct lineages of the virus isolated from minks points to ongoing adaptation of SARS-CoV-2 to a new host. The rapid acquisition and spread of SARS-CoV-2 mutations in minks suggests that if a similar phenomenon of host adaptation had occurred upon its jump into humans, those human-specific mutations would likely have reached fixation already before the first SARS-CoV-2 genomes were generated. ### Competing Interest Statement The authors have declared no competing interest.

9: Mutation rate variations in the human genome are encoded in DNA shape
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Posted 18 Jan 2021

Mutation rate variations in the human genome are encoded in DNA shape
11 tweets bioRxiv genomics

Zian Liu, Md Abul Hassan Samee

Single nucleotide mutation rates have critical implications for human evolution and genetic diseases. Accurate modeling of these mutation rates has long remained an open problem since the rates vary substantially across the human genome. A recent model, however, explained much of the variation by considering higher order nucleotide interactions in the local (7-mer) sequence context around mutated nucleotides. Despite this model's predictive value, we still lack a clear understanding of the biophysical mechanisms underlying the variations in genome-wide mutation rates. DNA shape features are geometric measurements of DNA structural properties, such as helical twist and tilt, and are known to capture information on interactions between neighboring nucleotides within a local context. Motivated by this characteristic of DNA shape features, we used them to model mutation rates in the human genome. These DNA shape feature based models improved both the accuracy (up to 14%) and the interpretability over the current nucleotide sequence-based models. The models also discovered the specific shape features that capture the most variability in mutation rates, and distinguished between the most and the least mutated sequence contexts, thus characterizing mutation promoting properties of the genomic DNA. To our knowledge, this is the first attempt that demonstrates the structural underpinnings of nucleotide mutations in the human genome and lays the groundwork for future studies to incorporate DNA shape information in modeling genetic variations.

10: The case for formal methodology in scientific reform
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Posted 28 Apr 2020

The case for formal methodology in scientific reform
11 tweets bioRxiv scientific communication and education

Berna Devezer, Danielle J. Navarro, Joachim Vandekerckhove, Erkan Ozge Buzbas

Current attempts at methodological reform in sciences come in response to an overall lack of rigor in methodological and scientific practices in experimental sciences. However, most methodological reform attempts suffer from similar mistakes and over-generalizations to the ones they aim to address. We argue that this can be attributed in part to lack of formalism and first principles. Considering the costs of allowing false claims to become canonized, we argue for formal statistical rigor and scientific nuance in methodological reform. To attain this rigor and nuance, we propose a five-step formal approach for solving methodological problems. To illustrate the use and benefits of such formalism, we present a formal statistical analysis of three popular claims in the metascientific literature: (a) that reproducibility is the cornerstone of science; (b) that data must not be used twice in any analysis; and (c) that exploratory projects imply poor statistical practice. We show how our formal approach can inform and shape debates about such methodological claims.

11: The lncRNA APOLO interacts with the transcription factor WRKY42 to trigger root hair cell expansion in response to cold
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Posted 14 Jul 2020

The lncRNA APOLO interacts with the transcription factor WRKY42 to trigger root hair cell expansion in response to cold
11 tweets bioRxiv plant biology

Michaël Moison, Javier Martínez Pacheco, Leandro Lucero, Camille Fonouni-Farde, Johan Rodríguez-Melo, Natanael Mansilla, Aurélie Christ, Jérémie Bazin, Moussa Benhamed, Fernando Ibañez, Martin Crespi, Jose Estevez, Federico Ariel

Plant long noncoding RNAs (lncRNAs) have emerged as important regulators of chromatin dynamics, impacting on transcriptional programs leading to different developmental outputs. The lncRNA AUXIN REGULATED PROMOTER LOOP ( APOLO ) directly recognizes multiple independent loci across the Arabidopsis genome and modulates their three-dimensional chromatin conformation, leading to transcriptional shifts. Here, we show that APOLO recognizes the locus encoding the root hair (RH) master regulator ROOT HAIR DEFECTIVE 6 (RHD6) and controls RHD6 transcriptional activity leading to cold-enhanced RH elongation. Furthermore, we demonstrate that APOLO interacts with the transcription factor WRKY42 and modulates its binding to the RHD6 promoter. WRKY42 is required for the activation of RHD6 by low temperatures and WRKY42 deregulation impairs cold-induced RH expansion. Collectively, our results indicate that a novel ribonucleoprotein complex involving APOLO and WRKY42 forms a regulatory hub which activates RHD6 by shaping its epigenetic environment and integrates signals governing RH growth and development.

12: Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK
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Posted 23 Sep 2020

Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK
11 tweets bioRxiv microbiology

Margaret J Hosie, Ilaria Epifano, Vanessa Herder, Richard J. Orton, Andrew Stevenson, Natasha Johnson, Emma MacDonald, Dawn Dunbar, Michael McDonald, Fiona Howie, Bryn Tennant, Darcy Herrity, Ana Da Silva Filipe, Daniel G. Streicker, Brian J Willett, Pablo Murcia, Ruth F Jarrett, David L. Robertson, William Weir, the COVID-19 Genomics UK (COG-UK) consortium

Two cats from different COVID-19-infected households in the UK were found to be infected with SARS-CoV-2 from humans, demonstrated by immunofluorescence, in situ hybridisation, reverse transcriptase quantitative PCR and viral genome sequencing. Lung tissue collected post-mortem from cat 1 displayed pathological and histological findings consistent with viral pneumonia and tested positive for SARS-CoV-2 antigens and RNA. SARS-CoV-2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the virus from cat 2 revealed that the feline viral genome contained five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS-CoV-2 sequence. An analysis of cat 2’s viral genome together with nine other feline-derived SARS-CoV-2 sequences from around the world revealed no shared catspecific mutations. These findings indicate that human-to-cat transmission of SARS-CoV-2 occurred during the COVID-19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the versatility of the new coronavirus, it will be important to monitor for human-to-cat, cat-to-cat and cat-to-human transmission. ### Competing Interest Statement The authors have declared no competing interest.

13: Investigating the impact of reference assembly choice on genomic analyses in a cattle breed
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Posted 17 Jan 2021

Investigating the impact of reference assembly choice on genomic analyses in a cattle breed
11 tweets bioRxiv genomics

Audald Lloret-Villas, Meenu Bhati, Naveen Kumar Kadri, Ruedi Fries, Hubert Pausch

Background: Reference-guided read alignment and variant genotyping are prone to reference allele bias, particularly for samples that are greatly divergent from the reference genome. A Hereford-based assembly is the widely accepted bovine reference genome. Haplotype-resolved genomes that exceed the current bovine reference genome in quality and continuity have been assembled for different breeds of cattle. Using whole genome sequencing data of 161 Brown Swiss cattle, we compared the accuracy of read mapping and sequence variant genotyping as well as downstream genomic analyses between the bovine reference genome (ARS-UCD1.2) and a highly continuous Angus-based assembly (UOA Angus 1). Results: Read mapping accuracy did not differ notably between the ARS-UCD1.2 and UOA Angus 1 assemblies. We discovered 22,744,517 and 22,559,675 high-quality variants from ARS-UCD1.2 and UOA Angus 1, respectively. The concordance between sequence- and array-called genotypes was high and the number of variants deviating from Hardy-Weinberg proportions was low at segregating sites for both assemblies. More artefactual INDELs were genotyped from UOA Angus 1 than ARS-UCD1.2 alignments. Using the composite likelihood ratio test, we detected 40 and 33 signatures of selection from ARS-UCD1.2 and UOA Angus 1, respectively, but the overlap between both assemblies was low. Using the 161 sequenced Brown Swiss cattle as a reference panel, we imputed sequence variant genotypes into a mapping cohort of 30,499 cattle that had microarray-derived genotypes. The accuracy of imputation (Beagle R2) was very high (0.87) for both assemblies. Genome-wide association studies between imputed sequence variant genotypes and six dairy traits as well as stature produced almost identical results from both assemblies. Conclusions: The ARS-UCD1.2 and UOA Angus 1 assemblies are suitable for reference-guided genome analyses in Brown Swiss cattle. Although differences in read mapping and genotyping accuracy between both assemblies are negligible, the choice of the reference genome has a large impact on detecting signatures of selection using the composite likelihood ratio test. We developed a workflow that can be adapted and reused to compare the impact of reference genomes on genome analyses in various breeds, populations and species.

14: FiCoS: a fine- and coarse-grained GPU-powered deterministic simulator for biochemical networks
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Posted 17 Jan 2021

FiCoS: a fine- and coarse-grained GPU-powered deterministic simulator for biochemical networks
10 tweets bioRxiv systems biology

Andrea Tangherloni, Marco S. Nobile, Paolo Cazzaniga, Giulia Capitoli, Simone Spolaor, Leonardo Rundo, Giancarlo Mauri, Daniela Besozzi

Mathematical models of biochemical networks can largely facilitate the comprehension of the mechanisms at the basis of cellular processes, as well as the formulation of hypotheses that can then be tested with targeted laboratory experiments. However, two issues might hamper the achievement of fruitful outcomes. On the one hand, detailed mechanistic models can involve hundreds or thousands of molecular species and their intermediate complexes, as well as hundreds or thousands of chemical reactions, a situation generally occurring when rule-based models are analysed. On the other hand, the computational analysis of a model typically requires the execution of a large number of simulations for its calibration or to test the effect of perturbations. As a consequence, the computational capabilities of modern Central Processing Units can be easily overtaken, possibly making the modeling of biochemical networks a worthless or ineffective effort. To the aim of overcoming the limitations of the current state-of-the-art simulation approaches, we present in this paper FiCoS, a novel "black- box" deterministic simulator that effectively realizes both a fine- and a coarse-grained parallelization on Graphics Processing Units. In particular, FiCoS exploits two different integration methods, namely the Dormand-Prince and the Radau IIA, to efficiently solve both non-stiff and stiff systems of coupled Ordinary Differential Equations. We tested the performance of FiCoS against different deterministic simulators, by considering models of increasing size and by running analyses with increasing computational demands. FiCoS was able to dramatically speedup the computations up to 855x, showing to be a promising solution for the simulation and analysis of large- scale models of complex biological processes.

15: Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag
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Posted 31 Jan 2020

Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag
10 tweets bioRxiv evolutionary biology

Prashant Pradhan, Ashutosh Kumar Pandey, Akhilesh Mishra, Parul Gupta, Praveen Kumar Tripathi, Manoj Balakrishnan Menon, James Gomes, Perumal Vivekanandan, Bishwajit Kundu

This paper has been withdrawn by its authors. They intend to revise it in response to comments received from the research community on their technical approach and their interpretation of the results. If you have any questions, please contact the corresponding author.

16: Formation and Spontaneous Long-Term Repatterning of Headless Planarian Flatworms
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Posted 17 Jan 2021

Formation and Spontaneous Long-Term Repatterning of Headless Planarian Flatworms
9 tweets bioRxiv developmental biology

Johanna Bischof, Jennifer LaPalme, Kelsie Miller, Junji Morokuma, Kate Williams, Chris Fields, Michael Levin

Regeneration requires the production of large numbers of new cells, and thus cell division regulators, particularly ERK signaling, are critical in regulating this process. In the highly regenerative planarian flatworm, questions remain as to whether ERK signaling controls overall regeneration or plays a head-specific role. Here we show that ERK inhibition in the 3 days following amputation delays regeneration, but that all tissues except the head can overcome this inhibition, resulting in headless regenerates. This prevention of head regeneration happens to a different degree along the anterior-posterior axis, with very anterior wounds regenerating heads even under ERK inhibition. Remarkably, 4 to 18 weeks after injury, the headless animals induced by ERK inhibition remodel to regain single-headed morphology, in the absence of further injury, in a process driven by Wnt/{beta}-catenin signaling. Interestingly, headless animals are likely to exhibit unstable axial polarity, and cutting or fissioning prior to remodeling can result in body-wide reversal of anterior-posterior polarity. Our data reveal new aspects of how ERK signaling regulates regeneration in planaria and show anatomical remodeling on very long timescales.

17: MAJORA: Continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance
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Posted 07 Oct 2020

MAJORA: Continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance
8 tweets bioRxiv bioinformatics

Samuel M. Nicholls, Radoslaw Poplawski, Matthew J. Bull, Anthony Underwood, Michael Chapman, Khalil Abu-Dahab, Ben Taylor, Ben Jackson, Sara Rey, Roberto Amato, Rich Livett, Sónia Gonçalves, Ewan M. Harrison, Sharon J Peacock, David Aanensen, Andrew Rambaut, Thomas R. Connor, Nick J Loman, The COVID-19 Genomics UK (COG-UK) Consortium

Genomic epidemiology has become an increasingly common tool for epidemic response. Recent technological advances have made it possible to sequence genomes rapidly enough to inform outbreak response, and cheaply enough to justify dense sampling of even large epidemics. With increased availability of sequencing it is possible for agile networks of sequencing facilities to collaborate on the sequencing and analysis of epidemic genomic data. In response to the ongoing SARS-CoV-2 pandemic in the United Kingdom, the COVID-19 Genomics UK (COG-UK) consortium was formed with the aim of rapidly sequencing SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of Majora, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network. The system was designed and implemented pragmatically to stand up capacity rapidly in a pandemic caused by a novel virus. This approach has underpinned the success of COG-UK, which has rapidly become the leading contributor of SARS-CoV-2 genomes to international databases and has generated over 60,000 sequences to date. ### Competing Interest Statement The authors have declared no competing interest.

18: Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart
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Posted 02 Jul 2020

Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart
8 tweets bioRxiv developmental biology

Thomas J Cahill, Xin Sun, Christophe Ravaud, Cristina Villa del Campo, Konstantinos Klaourakis, Irina-Elena Lupu, Allegra M Lord, Cathy Browne, Sten Eirik W Jacobsen, David R Greaves, David G Jackson, Sally A. Cowley, William James, Robin P Choudhury, Joaquim Miguel Vieira, Paul R. Riley

Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that resident macrophages in the subepicardial compartment of the developing heart coincide with the emergence of new lymphatics and interact closely with the nascent lymphatic capillaries. Consequently, global macrophage-deficiency led to extensive vessel disruption with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and fetal liver. Moreover, Csf1r+ and Cx3cr1+ myeloid sub-lineages were found to play essential functions in the remodeling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was found to be required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.

19: TP53 copy number expansion correlates with the evolution of increased body size and an enhanced DNA damage response in elephants
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Posted 06 Oct 2015

TP53 copy number expansion correlates with the evolution of increased body size and an enhanced DNA damage response in elephants
8 tweets bioRxiv genetics

Michael Sulak, Lindsey Fong, Katelyn Mika, Sravanthi Chigurupati, Lisa Yon, Nigel P. Mongan, Richard D. Emes, Vincent J. Lynch

A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as "Peto′s Paradox". Here we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes in the elephant (Proboscidean) lineage. Furthermore we show that several of the TP53 retrogenes are transcribed and translated and contribute to an enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis via a hyperactive TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes and the resolution of Peto′s paradox in Proboscideans.

20: Effective variant filtering and expected candidate variant yield in studies of rare human disease
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Posted 14 Aug 2020

Effective variant filtering and expected candidate variant yield in studies of rare human disease
7 tweets bioRxiv bioinformatics

Brent S Pedersen, Joseph Brown, Harriet Dashnow, Amelia D Wallace, Matt Velinder, Tatiana Tvrdik, Rong Mao, D. Hunter Best, Pinar Bayrak-Toydemir, Aaron Quinlan

In studies of families with rare disease, it is common to screen for de novo mutations, as well as recessive or dominant variants that explain the phenotype. However, the filtering strategies and software used to prioritize high-confidence variants vary from study to study. In an effort to establish recommendations for rare disease research, we derive effective guidelines for variant filtering and report the expected number of candidates for de novo dominant and recessive modes of inheritance. The filters are applied to common attributes, including genotype quality, sequencing depth, allele balance, and population allele frequency. The resulting guidelines yield approximately 10 candidate SNP and INDEL variants per exome, and 19 per genome. For whole genomes, this includes an average of three de novo , ten compound-heterozygotes, one autosomal recessive, four X-linked variants, and roughly 100 candidate variants following autosomal dominant inheritance. The slivar software we developed to establish and rapidly apply these filters to VCF files is available at <https://github.com/brentp/slivar> under an MIT license, and includes documentation and recommendations for best practices for rare disease analysis. ### Competing Interest Statement The authors have declared no competing interest.

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