Top 10 Biorxiv Papers Today in Genomics


2.068 Mikeys
#1. Rational reprogramming of cellular states by combinatorial perturbation
Jialei Duan, Boxun Li, Minoti Bhakta, Shiqi Xie, Pei Zhou, Nikhil Munshi, Gary Hon
Ectopic expression of transcription factors (TFs) can reprogram cell state. However, due to the large combinatorial space of possible TF cocktails, it remains difficult to identify TFs that reprogram specific cell types. Here, we develop Reprogram-Seq to experimentally screen thousands of TF cocktails for reprogramming performance. Reprogram-Seq leverages organ-specific cell atlas data with single-cell perturbation and computational analysis to predict, evaluate, and optimize TF combinations that reprogram a cell type of interest. Focusing on the cardiac system, we perform Reprogram-Seq on MEFs using an undirected library of 48 cardiac factors and separately on a directed library of 10 epicardial-related TFs. We identify a novel combination of 3 TFs which efficiently reprogram MEFs to epicardial-like cells that are transcriptionally, molecularly, morphologically, and functionally similar to primary epicardial cells. Reprogram-Seq holds promise to accelerate the generation of specific cell types for regenerative medicine.
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biorxivpreprint: Rational reprogramming of cellular states by combinatorial perturbation https://t.co/2l961ZgWEH #bioRxiv
biorxiv_genomic: Rational reprogramming of cellular states by combinatorial perturbation https://t.co/OAASQGHz0w #biorxiv_genomic
YSPTSPS: Rational reprogramming of cellular states by combinatorial perturbation | bioRxiv https://t.co/1eBdKUlk0y
timoast: Rational reprogramming of cellular states by combinatorial perturbation from @hon_lab: predict, evaluate, and optimize TF combinations that reprogram a cell type of interest https://t.co/A8Zp87bt9X
hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbation. Fun project and awesome collaboration with Nik Munshi. @BoxunLincolnLi @jlduan @CRSM_UTSW
bloodandtime1: 'Unbiased' single cell screening for in vitro direct conversions with TF libraries. This technology does not eliminate the need to build and curate a library of candidate TFs, but streamlines downstream readouts. https://t.co/fRak1BGbkE
generegulation: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
dkjhaunc: RT @YSPTSPS: Rational reprogramming of cellular states by combinatorial perturbation | bioRxiv https://t.co/1eBdKUlk0y
successprocess: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
steinaerts: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
Alexis_Lomakin: RT @YSPTSPS: Rational reprogramming of cellular states by combinatorial perturbation | bioRxiv https://t.co/1eBdKUlk0y
dbgoodman: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
SBLabUCSF: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
o_ursu: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
DavidPCook: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
JianXuLab: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
stranddw: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
SandraOrtizCua: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
ian_mellis: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
DavidDeGraff5: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
vincentpasque: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
rallanlab: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
PeterLyLab: RT @hon_lab: https://t.co/noGRjZ8b3r Excited to share our latest work. Rational reprogramming of cellular states by combinatorial perturbat…
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Sample Sizes : None.
Authors: 7
Total Words: 15201
Unqiue Words: 3544

2.037 Mikeys
#2. Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease
Mikko Konki, Maia Malonzo, Ida Karlsson, Noora Lindgren, Bishwa Ghimire, Johannes Smolander, Noora Scheinin, Miina Ollikainen, Asta Laiho, Laura L. Elo, Tapio Lönnberg, Matias Röyttä, Nancy Pedersen, Jaakko Kaprio, Harri Lähdesmäki, Juha Rinne, Riikka J Lund
Alzheimer's disease (AD) results from a neurodegenerative process that starts well before the diagnosis can be made. New prognostic or diagnostic markers enabling early intervention into the disease process would be highly valuable. As life style factors largely modulate the disease risk, we hypothesised that the disease associated DNA methylation signatures are detectable in the peripheral blood of discordant twin pairs. Reduced Representation Bisulfite Sequencing, single cell RNA-sequencing and gene array data were utilised to examine DNA methylation signatures and associated gene expression changes in blood and hippocampus, and targeted bisulfite sequencing in cross cohort validation. Our results reveal that discordant twin pairs have disease associated differences in their peripheral blood epigenomes. A subset of affected genes, e.g. ADARB2 contain differentially methylated sites also in anterior hippocampus. The DNA methylation differences seem to influence gene expression in brain rather than in blood cells. The affected...
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biorxivpreprint: Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease https://t.co/ifeiHSSznU #bioRxiv
biorxiv_genomic: Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease https://t.co/HhxpcnXj7o #biorxiv_genomic
westr: Peripheral blood DNA methylation differences in #twin pairs discordant for #Alzheimer's disease https://t.co/UKRwIVbL2t
TheFirstNuomics: https://t.co/NCjfchWVdY
mtmdphd: RT @westr: Peripheral blood DNA methylation differences in #twin pairs discordant for #Alzheimer's disease https://t.co/UKRwIVbL2t
tangming2005: RT @biorxivpreprint: Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease https://t.co/ifeiHSSznU…
NicoleKuderer: RT @westr: Peripheral blood DNA methylation differences in #twin pairs discordant for #Alzheimer's disease https://t.co/UKRwIVbL2t
ScienceRad: RT @westr: Peripheral blood DNA methylation differences in #twin pairs discordant for #Alzheimer's disease https://t.co/UKRwIVbL2t
GeneticLifehack: RT @biorxivpreprint: Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease https://t.co/ifeiHSSznU…
pickettbd: RT @biorxivpreprint: Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease https://t.co/ifeiHSSznU…
jenny_vandongen: RT @biorxiv_genomic: Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease https://t.co/HhxpcnXj7o…
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Sample Sizes : [9, 7, 8, 7]
Authors: 17
Total Words: 9423
Unqiue Words: 3018

2.019 Mikeys
#3. Unbiased genome-scale identification of cis-regulatory modules in the human genome by GRAMc
Catherine L Guay, Jongmin Nam
Although significant advances have been made toward functionally identifying human regulatory elements, existing genome-scale reporter methods preferentially detect either enhancers or promoters. Here we develop GRAMc, a highly reproducible unbiased Genome-scale Reporter Assay Method for cis-regulatory modules (CRMs). GRAMc combines the versatility of traditional reporter constructs and the scalability of DNA barcode reporters, and unites the complementary advantages of several currently available high-throughput reporter assays. We demonstrate that GRAMc can reliably measure cis-regulatory activity of nearly 90% of the human genome in 200 million HepG2 cells with randomly fragmented ~800bp inserts. By using the GRAMc-identified CRMs, we show that CRMs identified in one cell type are useful for predicting gene regulatory programs not only within that cell type but also between cell types or conditions separated in time and space. In addition, the GRAMc-identified CRMs support the hypothesis that SINE/Alu elements are rich sources...
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biorxivpreprint: Unbiased genome-scale identification of cis-regulatory modules in the human genome by GRAMc https://t.co/WRHuZheLAZ #bioRxiv
biorxiv_genomic: Unbiased genome-scale identification of cis-regulatory modules in the human genome by GRAMc https://t.co/FQQI1Dyrza #biorxiv_genomic
alex_marand: Another STARR-seq variant that shows promise. https://t.co/b5FTmPjGVl
Schmitz_Lab: RT @alex_marand: Another STARR-seq variant that shows promise. https://t.co/b5FTmPjGVl
dajiangliu81: RT @biorxiv_genomic: Unbiased genome-scale identification of cis-regulatory modules in the human genome by GRAMc https://t.co/FQQI1Dyrza #…
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Authors: 2
Total Words: 17859
Unqiue Words: 4325

2.002 Mikeys
#4. High-resolution mapping of regulatory element interactions and genome architecture using ARC-C
Ni Huang, Wei Qiang Seow, Julie Ahringer
Interactions between cis-regulatory elements such as promoters and enhancers are important for transcription but global identification of these interactions remains a major challenge. Leveraging the chromatin accessiblity of regulatory elements, we developed ARC-C (accessible region chromosome conformation capture), which profiles chromatin regulatory interactions genome-wide at high resolution. Applying ARC-C to C. elegans, we identify ~15,000 significant interactions at 500bp resolution. Regions bound by transcription factors and chromatin regulators such as cohesin and condensin II are enriched for interactions, and we use ARC-C to show that the BLMP-1 transcription factor mediates interactions between its targets. Investigating domain level architecture, we find that C. elegans chromatin domains defined by either active or repressive modifications form topologically associating domains (TADs) and that these domains interact with A/B (active/inactive) compartment structure. ARC-C is a powerful new tool to interrogate genome...
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Tweets
biorxivpreprint: High-resolution mapping of regulatory element interactions and genome architecture using ARC-C https://t.co/26s4sStXsc #bioRxiv
biorxiv_genomic: High-resolution mapping of regulatory element interactions and genome architecture using ARC-C https://t.co/TtSs00Czf3 #biorxiv_genomic
razoralign: High-resolution mapping of regulatory element interactions and genome architecture using ARC-C: https://t.co/DEZabQEbES https://t.co/OpEzsWja7y
GIS_Sharer: RT @razoralign: High-resolution mapping of regulatory element interactions and genome architecture using ARC-C: https://t.co/DEZabQEbES htt…
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Sample Sizes : [42245, 5124, 2224, 879]
Authors: 3
Total Words: 8114
Unqiue Words: 2335

2.0 Mikeys
#5. Long-read viral metagenomics enables capture of abundant and microdiverse viral populations and their niche-defining genomic islands
Joanna Warwick-Dugdale, Natalie Solonenko, Karen Moore, Lauren Chittick, Ann C Gregory, Michael J Allen, Matthew B Sullivan, Ben Temperton
Marine viruses impact global biogeochemical cycles via their influence on host community structure and function, yet our understanding of viral ecology is constrained by limitations in culturing of important hosts and the lack of a universal gene to facilitate community surveys. Short-read viral metagenomic studies have provided clues to viral function and first estimates of global viral gene abundance and distribution. However, short-read assemblies are confounded by populations with high levels of strain evenness and nucleotide diversity (microdiversity), limiting assembly of some of the most abundant viruses on Earth. Assembly across genomic islands which likely contain niche-defining genes that drive ecological speciation is also challenging. While such populations and features are successfully captured by single-virus genomics and fosmid-based approaches, both techniques require considerable cost and technical expertise. Here we established a low-cost, low-input, high throughput alternative method for improving assembly of...
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yokadzaki: Long-read viral metagenomics enables capture of abundant and microdiverse viral populations and their niche-defining genomic islands https://t.co/AHJLDEfWRK
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Sample Sizes : [1500]
Authors: 8
Total Words: 13471
Unqiue Words: 3538

2.0 Mikeys
#6. Single-nuclei RNA-seq on human retinal tissue provides improved transcriptome profiling.
Qingnan Liang, Rachayata Dharmat, Leah Owen, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Nathaniel Wu, Margaret DeAngelis, Rui Chen
The retina is the innermost layer of tissue in the eyes of human and most other vertebrates. It receives the information of the visual images like the film of a camera, translates the images into neural signals, and transduces the signal to the brain. Three layers of neural cells (photoreceptor cells, bipolar cells, and ganglion cells) within the retina are comprised of seven major cell types; rod, cone, Muller glia cell, amacrine cell, horizontal cell, bipolar cell, and retinal ganglion cells, which create visual perception through functional cooperation. In all retinal diseases, it is the ultimate degeneration of the photoreceptors, the rods and cones, which results in blindness. Understanding all the individual cell types and how they contribute the basic neural circuitry in both the human and mouse retina will be key to elucidating the mechanism of retinal degenerations. Here, we report to the best of our knowledge the first single-nuclei RNA-seq based transcriptomic study on the human neural retinal tissue. We sequenced 6544...
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TheFirstNuomics: https://t.co/ZsaaXoQlDo
Psy_Fer_: RT @biorxiv_genomic: Single-nuclei RNA-seq on human retinal tissue provides improved transcriptome profiling. https://t.co/g4P2Kavv3W #bio…
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Authors: 12
Total Words: 9581
Unqiue Words: 3269

1.998 Mikeys
#7. First Draft Genome of a Brazilian Atlantic Rainforest Burseraceae reveals commercially-promising genes involved in terpenic oleoresins synthesis
Luana Ferreira Afonso, Danielle Amaral, Marcela Uliano-Silva, André Luiz Quintanilha Torres, Daniel Reis Simas, Mauro de Freitas Rebelo
Background: Protium species produce abundant aromatic oleoresins composed mainly of different types of terpenes, which are highly sought after by the flavor and fragrance industry. Results: Here we present (i) the first draft genome of an endemic tree of the Brazil's Atlantic Rainforest (Mata Atlântica), Protium kleinii Cuatrec., (ii) a first characterization of its genes involved in the terpene pathways, and (iii) the composition of the resin's volatile fraction. The de novo draft genome was assembled using Illumina paired-end-only data, totalizing 407 Mb in size present in 229,912 scaffolds. The N50 is 2.60 Kb and the longest scaffold is 52.26 Kb. Despite its fragmentation, we were able to infer 53,538 gene models of which 5,434 were complete. The draft genome of P. kleinii presents 76.67 % (62.01 % completes and 14.66 % partial) of plant-core BUSCO genes. InterProScan was able to assign at least one Gene Ontology annotation and one Pfam domain for 13,629 and 26,469 sequences, respectively. We were able to identify 116 enzymes...
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Authors: 6
Total Words: 7280
Unqiue Words: 2834

1.998 Mikeys
#8. Refining interaction search through signed iterative Random Forests
Karl Kumbier, Sumanta Basu, James B Brown, Susan Celniker, Bin Yu
Advances in supervised learning have enabled accurate prediction in biological systems governed by complex interactions among biomolecules. However, state-of-the-art predictive algorithms are typically "black-boxes," learning statistical interactions that are difficult to translate into testable hypotheses. The iterative Random Forest (iRF) algorithm took a step towards bridging this gap by providing a computationally tractable procedure to identify the stable, high-order feature interactions that drive the predictive accuracy of Random Forests (RF). Here we refine the interactions identified by iRF to explicitly map responses as a function of interacting features. Our method, signed iRF (s-iRF), describes subsets of rules that frequently occur on RF decision paths. We refer to these "rule subsets" as signed interactions. Signed interactions share not only the same set of interacting features but also exhibit similar thresholding behavior, and thus describe a consistent functional relationship between interacting features and...
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seandavis12: Refining interaction search through signed iterative Random Forests https://t.co/hLZXzvKtgt
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Authors: 5
Total Words: 12653
Unqiue Words: 3153

1.998 Mikeys
#9. Transcription-factor centric genome mining strategy for discovery of diverse unprecedented RiPP gene clusters
Shaozhou Zhu, Guojun Zheng
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly emerging group of natural products with diverse biological activity. Most of their biosynthetic mechanisms are well studied and the genome mining strategy based on homology has led to the unearthing of many new ribosomal natural products, including lantipeptides, lasso peptides, cyanobactins. These precursor-centric or biosynthetic protein-centric genome mining strategies have encouraged the discovery of RiPPs natural products. However, a limitation of these strategies is that the newly identified natural products are similar to the known products and novel families of RiPP pathways were overlooked by these strategies. In this work, we applied a transcription-factor centric genome mining strategy and diverse unique crosslinked RiPP gene clusters were predicted in several sequenced microorganisms. Our research could significantly expand the category of biosynthetic pathways of RiPP natural products and predict new resources for novel RiPPs.
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Authors: 2
Total Words: 7105
Unqiue Words: 2139

1.998 Mikeys
#10. Substructured population growth in the Ashkenazi Jews inferred with Approximate Bayesian Computation
Ariella L Gladstein, Michael F Hammer
The Ashkenazi Jews (AJ) are a population isolate that have resided in Central Europe since at least the 10th century and share ancestry with both European and Middle Eastern populations. Between the 11th and 16th centuries, AJ expanded eastward leading to two culturally distinct communities, one in central Europe and one in eastern Europe. Our aim was to determine if there are genetically distinct AJ subpopulations that reflect the cultural groups, and if so, what demographic events contributed to the population differentiation. We used Approximate Bayesian Computation (ABC) to choose among models of AJ history and infer demographic parameter values, including divergence times, effective population size, and gene flow. For the ABC analysis we used allele frequency spectrum and identical by descent based statistics to capture information on a wide timescale. We also mitigated the effects of ascertainment bias when performing ABC on SNP array data by jointly modeling and inferring the SNP discovery. We found that the most likely...
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Sample Sizes : [19, 239]
Authors: 2
Total Words: 8196
Unqiue Words: 2751

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