Tag: TSS

Pacritinib Shows Transfusion Independence Benefits in Myelofibrosis

Bart Scott, MD Professor, Transplantation Program Clinical Research Division Miklos Kohary and Natalia Zimonyi Kohary Endowed Chair Fred Hutchinson Cancer Center Seattle, WA Targeted Oncology: Could you summarize the approved Janus kinase (JAK) inhibitors for patients with myelofibrosis? BART SCOTT, MD: Ruxolitinib (Jakafi) was approved in 2011, fedratinib (Inrebic) in…

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UV Radiation and Its Impact on Plant Genome: Insights and Mechanisms

UV Radiation and Its Impact on Plant Genome Plants, as primary producers, rely on solar energy for photosynthesis, a vital process for their survival and growth. However, the UV component of solar radiation can impair genome stability in plants by creating DNA lesions known as UV photoproducts. These lesions hinder…

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Results of the MANIFEST-2 Randomized, Double-Blind, Phase 3 Study

Background Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and MF-associated symptoms. These hallmarks result from dysregulation of the JAK/STAT pathway and BET-mediated MF target gene modulation. Pelabresib (CPI-0610; pela) is an investigational oral small-molecule drug designed to inhibit BET-mediated gene transcription involved in MF pathogenesis. Preclinical data…

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Sequential deregulation of histone marks, chromatin accessibility and gene expression in response to PROTAC-induced degradation of ASH2L

Loss of ASH2L prevents cell proliferation We have studied the molecular and cellular consequences of Ash2l loss in mouse embryo fibroblasts (MEFs) with floxed Ash2l alleles and an inducible Cre-ER recombinase (iMEF-Ash2lfl/fl-Cre-ER). While the knockout of Ash2l was rapid, the downstream effects, including the decrease in promoter-associated H3K4me3, altered gene…

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Transcription factor-mediated direct cellular reprogramming yields cell-type specific DNA methylation signature

iISC-BOs exhibit a CpG methylation signature that closely resembles ISC-BOs Genomic DNA was extracted from MEFs, iISC-BOs, and ISC-BOs, and high-resolution methylome analysis was performed using the PBAT method (Fig. 1A). The genome-wide methylation states of cytosine-containing sequences such as CpG, CHH, and CHG were compared among the samples. The data…

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MorphoSys’ Pelabresib Improves All Four Hallmarks of Myelofibrosis in Phase 3 MANIFEST-2 Study

Pelabresib and ruxolitinib combination significantly reduced spleen size, with an SVR35 response rate nearly double that of placebo plus ruxolitinib Showed a strong positive trend in reducing symptom burden and a twofold increase in patients achieving both SVR35 and TSS50 versus placebo plus ruxolitinib Improved measures of anemia, including higher…

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MorphoSys AG? Pelabresib Improves All Four Hallmarks of Myelofibrosis in Phase 3 MANIFEST-2 Study -December 10, 2023 at 07:31 pm EST

MorphoSys AG announced comprehensive results from the Phase 3 MANIFEST-2 study investigating pelabresib, an investigational BET inhibitor, in combination with the JAK inhibitor ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis. These findings were presented in an oral presentation at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition…

Continue Reading MorphoSys AG? Pelabresib Improves All Four Hallmarks of Myelofibrosis in Phase 3 MANIFEST-2 Study -December 10, 2023 at 07:31 pm EST

Adding Navitoclax to Ruxolitinib Doubles Spleen Volume Reductions for Myelofibrosis

Up-front treatment with the combination of navitoclax and ruxolitinib (Jakafi) significantly reduced spleen volume by 35% or more at week 24 (SVR35W24) compared with ruxolitinib plus placebo for patients with myelofibrosis; however, a significant difference was not observed in total symptom score (TSS) version 4.0 between the arms, according to…

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CRISPRi gene modulation and all-optical electrophysiology in post-differentiated human iPSC-cardiomyocytes

A feasibility CRISPRi study was performed in post-differentiated iPSC-CMs targeting key genes important in cardiac electrophysiology. Comprehensive analysis using all-optical electrophysiology and a pipeline enabling correlative analysis of functional and molecular data in the same samples helped quantify the CRISPRi gene modulation in this in vitro model. Time-dependent control of…

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Functional conservation of specialized ribosomes bearing genome-encoded variant rRNAs in Vibrio species

Fig 1. rrnI-dependent expression of HspA in V. vulnificus MO6-24/O strains. (A) Schematic representation of the allele-specific RT-PCR analysis analyzing the relative amounts of I-rRNA or G-rRNA. (B) The number of I-rRNA or G-rRNA amplicons and other rRNAs amplified from the cDNA of the MO6 WT, MO6+rrnG, and MO6+rrnI strains…

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Organ-specific characteristics govern the relationship between histone code dynamics and transcriptional reprogramming during nitrogen response in tomato

A supply of nitrate triggers organ-specific changes of histone modifications at specific gene loci To investigate the organ specificity of dynamic histone modifications in response to N changes, we treated 3-week-old tomato seedlings (Solanum lycopersicum, cultivar M82) with four days of N starvation, followed by N-supply (2.8 mM NO3−; +N) or…

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Compute matrix skipping many regions stating not found in compute matrix output

Compute matrix skipping many regions stating not found in compute matrix output 0 Hello all I am working on Chip seq data and for generating the TSS Plots when I am computing the matrix it is giving a very long list stating “skipping NR_049895_r4, due to being absent in the…

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East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease

We conducted a three-stage genome-wide analysis of PUD and its subtypes. An overview of the workflow is provided in Fig. 1 and Supplementary Fig. 1. PUD cases in the east Asian populations were obtained by combining individuals with any of the two major PUD subtypes (DU and GU), which were…

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MorphoSys: A Buying Opportunity Following Mixed Phase 3 Results In Myelofibrosis (MOR)

tonaquatic Thesis overview MorphoSys AG (NASDAQ:MOR) recently announced positive topline results from its phase 3 trial of pelabresib in myelofibrosis (MF). The study easily met the primary endpoint. However, despite the strong positive trend, statistical significance was not achieved at key secondary endpoints assessing symptomatic improvement. Nevertheless, in a pre-specified…

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Chipseq peak calling and peak frequency region

I am working on Chip seq data, I have implemented the chipseq pipeline with spike in method and called peaks using MACS2. The same data has been analyzed before in my lab, and my peaks show a similar pattern as the previous ones . By this I meant that the…

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MorphoSys still plans to file myelofibrosis drug despite mixed Phase 3 results

An early readout of Phase 3 results for MorphoSys myelofibrosis agent pelabresib did more than raise the bar in this increasingly crowded treatment setting. Even though they’re not all good, the findings also solidified the company’s registrational plans. In the MANIFEST-2 trial in first-line myelofibrosis, pelabresib combined with Incyte’s JAK…

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Working with NCBI downloadable Datasets

Working with NCBI downloadable Datasets 0 Hi all, I’m an postgraduate student currently working on an assigment in the field of “Analysis Molecular Data”. We’ve been instructed to examine polymoprhism in the promoter of the gene MMP3 in humans, and how that might affect expression and causality for genetic disorders….

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Creating heatmap for ChIP-seq using deeptools

Hi all, I am a newbie in ChIP-seq, and I conducted my analysis using the nfcore ChIPseq pipeline. After reviewing the results, I now need to perform more specific analyses. With nfcore, I generated informative heatmaps that provide a general overview of my ChIP-seq data (I will upload the heatmap)….

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MorphoSys’ Phase 3 Study of Pelabresib in Myelofibrosis Demonstrates Statistically Significant Improvement in Spleen Volume Reduction and Strong Positive Trend in Symptom Reduction

Publication of an inside information according to Article 17 para. 1 of the Regulation (EU) No. 596/2014 MANIFEST-2 met primary endpoint, nearly doubling SVR35 response rate (66% versus 35%) The key secondary endpoints assessing symptom reduction, TSS50 and absolute change in TSS, showed significant improvements for intermediate-risk patients (p<0.05, p<0.02,…

Continue Reading MorphoSys’ Phase 3 Study of Pelabresib in Myelofibrosis Demonstrates Statistically Significant Improvement in Spleen Volume Reduction and Strong Positive Trend in Symptom Reduction

MorphoSys : Phase 3 Study Of Pelabresib Combination In Myelofibrosis Meets Primary Endpoint

(RTTNews) – MorphoSys AG (MOR) announced strong results from the Phase 3 MANIFEST-2 study investigating pelabresib, an investigational BET inhibitor, in combination with the JAK inhibitor ruxolitinib compared with placebo plus ruxolitinib in JAK inhibitor-nave patients with myelofibrosis. The company noted that the study met its primary endpoint, as the…

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MorphoSys AG Announces Strong Topline Results from the Phase 3 MANIFEST-2 Study Investigating Pelabresib -November 20, 2023 at 04:30 pm EST

MorphoSys AG announced strong topline results from the Phase 3 MANIFEST-2 study investigating pelabresib, an investigational BET inhibitor, in combination with the JAK inhibitor ruxolitinib compared with placebo plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis. MANIFEST-2 met its primary endpoint, as the combination therapy demonstrated a statistically significant and…

Continue Reading MorphoSys AG Announces Strong Topline Results from the Phase 3 MANIFEST-2 Study Investigating Pelabresib -November 20, 2023 at 04:30 pm EST

MorphoSys AG (MOR) Reports Phase 3 Study of Pelabresib in Myelofibrosis Demonstrates Statistically Significant Improvement in Spleen Volume Reduction and Strong Positive Trend in Symptom Reduction

MorphoSys AG (NASDAQ: MOR) today announced strong topline results from the Phase 3 MANIFEST-2 study investigating pelabresib, an investigational BET inhibitor, in combination with the JAK inhibitor ruxolitinib compared with placebo plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis. MANIFEST-2 met its primary endpoint, as the combination therapy demonstrated a…

Continue Reading MorphoSys AG (MOR) Reports Phase 3 Study of Pelabresib in Myelofibrosis Demonstrates Statistically Significant Improvement in Spleen Volume Reduction and Strong Positive Trend in Symptom Reduction

Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens

Developing an epigenetic screening platform in human T cells Staphylococcus aureus Cas9 (SaCas9) has been extensively used for genome editing in vivo as its compact size (3,159 bp) relative to the conventional Streptococcus pyogenes Cas9 (SpCas9) enables packaging into adeno-associated virus26,27,28. However, SaCas9 has not been widely used for targeted gene…

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the enrichment of TSS and TES region are similar when using scale-region

Wrong in Deeptools : the enrichment of TSS and TES region are similar when using scale-region 0 While using plotProfile to create enrichment for a Pol cut-tag dataset, I got similar enrichment peak around TSS and TES which actully will show higher enrichment in TSS than TES. So could someone…

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Nascent ribosomal RNA act as surfactant that suppresses growth of fibrillar centers in nucleolus

Transcription and RNA processing The occupancy \({n}_{{{{{{\rm{ps}}}}}}}\) of the TSS of the active rDNA by Pol I follows the kinetic equation $$\frac{d}{{dt}}{n}_{{{{{{\rm{ps}}}}}}}={k}_{{{{{{\rm{on}}}}}}}\rho \left(1-{n}_{{{{{{\rm{ps}}}}}}}\right)-{k}_{{{{{{\rm{off}}}}}}}{n}_{{{{{{\rm{ps}}}}}}}-{k}_{{{{{{\rm{e}}}}}}}{n}_{{{{{{\rm{ps}}}}}}}.$$ (5) Equation (5) suggests that the occupancy \({n}_{{{{{{\rm{ps}}}}}}}\) changes due to the binding of Pol I from the FC (the first term), the unbinding of Pol I…

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distance between chip peaks and individual TSS

distance between chip peaks and individual TSS 0 I have generated my peak data through chip sequencing data and I have individual transcription sites coordinates from RNA sequencing data. How to compare the distance between these TSS and peaks, so that I can find the closest TSS to peak and…

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Two days_to_last_followups encountered when conducting Survival Analysis with TCGA Clinical Data

Two days_to_last_followups encountered when conducting Survival Analysis with TCGA Clinical Data 0 I was conducting Survival Analysis to TCGA-LIHC project, and when I look through the clinical data I found that there are two days_to_last_followups tags. One of it belongs clin_shared:race_list,and the other lihc:follow_ups one that belongs to clin_shared:race_list <clin_shared:days_to_last_followup…

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DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle

Overview of this study In this study, we measured the DNA methylome from mouse liver and skeletal muscle, integrated the data with the transcriptome and proteome of these mouse tissues22,23, and examined how tissue-dominant protein and gene expression were associated with DNA hypomethylation (Fig. 1). In this study, we measured DNA…

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Karyopharm Therapeutics Reports Q3 2023 Financial Results, Highlights Strong Position for Growth By Investing.com

© Reuters. Karyopharm Therapeutics (NASDAQ: NASDAQ:) has reported its financial results for the third quarter of 2023, noting a strong position for growth backed by its pipeline of innovative oral selective inhibitors and nuclear export. The company expects total revenues of $145 million to $160 million in 2023, and anticipates…

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Structural Variants in gnomAD v4

Today, we are thrilled to announce the release of genome-wide structural variants (SVs) for 63,046 unrelated samples with genome sequencing (GS) data. All site-level information for 1,199,117 high-quality SVs discovered in these samples is browsable in the gnomAD browser (gnomAD SV v4) and downloadable from the gnomAD downloads page. For…

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MorphoSys To Showcase Phase 3 MANIFEST-2 Data on Pelabresib in Myelofibrosis in Oral Presentation at 2023 ASH Annual Meeting -November 02, 2023 at 09:07 am EDT

EQS-News: MorphoSys AG / Key word(s): Miscellaneous MorphoSys To Showcase Phase 3 MANIFEST-2 Data on Pelabresib in Myelofibrosis in Oral Presentation at 2023 ASH Annual Meeting 02.11.2023 / 14:05 CET/CESTThe issuer is solely responsible for the content of this announcement. Media Release Planegg/Munich, Germany, November 2, 2023   MorphoSys To…

Continue Reading MorphoSys To Showcase Phase 3 MANIFEST-2 Data on Pelabresib in Myelofibrosis in Oral Presentation at 2023 ASH Annual Meeting -November 02, 2023 at 09:07 am EDT

MorphoSys AG to Showcase Phase 3 MANIFEST-2 Data on Pelabresib in Myelofibrosis in Oral Presentation at 2023 ASH Annual Meeting -November 02, 2023 at 09:45 am EDT

MorphoSys AG announced that data from the Phase 3 MANIFEST-2 trial of pelabresib, an investigational BET inhibitor, in combination with the JAK inhibitor ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis will be presented during an oral presentation on Sunday, December 10, at the 65th American Society of Hematology (ASH) Annual…

Continue Reading MorphoSys AG to Showcase Phase 3 MANIFEST-2 Data on Pelabresib in Myelofibrosis in Oral Presentation at 2023 ASH Annual Meeting -November 02, 2023 at 09:45 am EDT

MorphoSys To Showcase Phase 3 MANIFEST-2 Data on Pelabresib in Myelofibrosis in Oral Presentation at 2023 ASH Annual Meeting

EQS-News: MorphoSys AG / Key word(s): Miscellaneous MorphoSys To Showcase Phase 3 MANIFEST-2 Data on Pelabresib in Myelofibrosis in Oral Presentation at 2023 ASH Annual Meeting 02.11.2023 / 14:05 CET/CESTThe issuer is solely responsible for the content of this announcement. Media Release Planegg/Munich, Germany, November 2, 2023   MorphoSys To…

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papain family cysteine protease containing protein, maker-scaffold1702_size30647-snap-gene-0.14 (gene) Tigriopus kingsejongensis

Associated RNAi Experiments Homology BLAST of papain family cysteine protease containing protein vs. L. salmonis genes Match: EMLSAG00000006045 (supercontig:LSalAtl2s:LSalAtl2s327:400616:404607:-1 gene:EMLSAG00000006045 transcript:EMLSAT00000006045 description:”augustus_masked-LSalAtl2s327-processed-gene-4.0″) HSP 1 Score: 590.497 bits (1521), Expect = 0.000e+0Identity = 283/525 (53.90%), Postives = 368/525 (70.10%), Query Frame = 0 Query: 49 GHVARPLGKSPPNFVRDPPPRTTPPAQWLWNNVNETNFLTVSRNQHLPTYCGSCWAHAATSSLSDRIKIARQGAWPDINLAPQVLISCGPGDGCHGGEAGDANAYMHAQGITDETCSIYRARGQDNGLPCSKLEICSTCE—SKCYQPQHFFTYRVDEFHDVEGESNGEQEANMMAEIHHRGPISCGIAVTQALV-NYTGGLFHDKTGAQEIDHDISVVGYGVDEGTQEKYWLIRNSWGTYWGEQGFFRLIRGVNNLGIESGTCSWATPADTWSDAARE—RAAILSNEITLQKP——LWKQLWTVVADFVDNTRDTDLFRRLKLMQKGCKKLSSPRVPVVNIRPRPQDYVSTADLPEALDWRSVNGTNFLSWSVNQHLPVYCGSCWAQAGLSSLADRFTIADRKRFANLALSVQYILNCQAGGSCHGGDAFPLYAFIQKQGVPDVTCQPYEALDEGPLTDCSKPSKLVCKDCTWPPPEPGQEGNCWAKEKFHRYYVDEYNGVEGADNMKKEILERGPVT 560 GH+ R G+…

Continue Reading papain family cysteine protease containing protein, maker-scaffold1702_size30647-snap-gene-0.14 (gene) Tigriopus kingsejongensis

Diet-induced rewiring of the Wnt gene regulatory network connects aberrant splicing to fatty liver and liver cancer in DIAMOND mice

DIAMOND mice develop HCC in the context of obesity and insulin resistance To investigate in depth the genome-wide transcriptional and epigenetic changes that occur during development of MAFLD and obesity-related hepatocellular carcinoma (HCC), we performed RNA-sequencing (RNA-seq) and Chromatin ImmunoPrecipitation-sequencing (ChIP-seq) of liver tumours (HCC) and liver control tissue (FL)…

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Ensembl transcript IDs

Ensembl transcript IDs 0 Hi everyone, From the GENCODE gtf file, I noticed that there are multiple ensembl transcript IDs for one gene ID and and one ensembl transcript id may have different versions (different values after the decimal). There are different transcript isoforms of one gene (due to alternative…

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MICA: a multi-omics method to predict gene regulatory networks in early human embryos

Introduction After the fusion of the oocyte and sperm, the zygote undergoes a series of cell divisions until it forms a blastocyst before implantation into the uterus. A human blastocyst is formed of a fluid-filled cavity and ∼200 cells that comprise three distinct cell types: the trophectoderm (TE), which gives…

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Genome-wide epigenetic dynamics during postnatal skeletal muscle growth in Hu sheep

Global changes of the transcriptome during postnatal muscle growth The number of myofibers is thought to remain fixed following birth, muscle fiber hypertrophy growth is the primaryway of muscle growth. The average CSA is generally used to measure the hypertrophy of skeletal muscle fibers. To systematically identify the growth of postnatal…

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Get the strongest TF binding regions for Chip-Seq

Get the strongest TF binding regions for Chip-Seq 0 Hi All, Is there a package / program that finds the peaks with the most differential pileup between the condition and input? For example, I am currently calling peaks with HOMER and MACS2; these programs automatically determine if the amount of…

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rstudio – Continuous treatment effect using twangContinuous

I was reading the tutorial for twangContinuous here: cran.r-project.org/web/packages/twangContinuous/vignettes/briefTutorial.html I loaded their dataset dat and say that there are two treatment groups A and B and there are different levels of tss_0 is their continuous exposure and represents a count of trauma symptoms. Both treatment groups include 0<=tss_0<=13. 0 0.1…

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Google Adds Broad Generative AI Indemnity, But You Might Want to Note the Exceptions

Google announced that it has added specific language providing clarity around indemnification for generative AI services last week, and has benefitted from numerous favorable headlines. However, if you take a look at the updated terms of service (TOS) you will notice several exceptions that will get the attention of corporate…

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DNA methylation: The hidden mechanism enablin

image:  Experimental setup and phenotypic responses under common garden-conditions in Fragaria vesca plants after propagation at different temperatures for up to three asexual generations. view more  Credit: Horticulture Research As global warming continues to redefine ecosystems, plants are increasingly tasked with swift adaptation to ensure their survival. One primary mechanism…

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Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin

Mapping eQTLs in patients with psoriasis We obtained longitudinal lesional and non-lesional skin biopsies from participants at baseline, during treatment, and at the time of psoriasis relapse after study medication withdrawal over a course of 22 months. We used genome-wide genotyping and RNA-seq to assay samples. After stringent quality control,…

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A versatile regulatory toolkit of arabinose-inducible artificial transcription factors for Enterobacteriaceae

Design of arabinose-inducible artificial transcription factors A core objective of our work was to develop inducible, heterologous regulators capable of genetically reprogramming gene regulatory networks in Enterobacteriaceae, specifically Salmonella and E. coli. To achieve this, we designed arabinose-inducible ATFs incorporating diverse DBDs originating from CRISPR/dCas9 and plant heterologous TFs (Fig. 1)….

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DEG gene list and find common TF from public ChlP-Seq data

DEG gene list and find common TF from public ChlP-Seq data 0 RNA-seq of treated sample gave me a list of DEG genes. am trying to find what transcriptional factor do these DEG have in common. have a bed file that contains all the publicly available TF ChiP-seq of a…

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to annotate BEDPE files

to annotate BEDPE files 0 Dear all, a simple question if I may ask you please : given a BEDPE file (a short example is shown below), which tools would you recommend for computing the annotations for END1 and END2 (in order to annotate with the closest TSS, closest TTS,…

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Comparing multiple columns from two files using AWK

Dear all, I need your help to solve the following problem. I have the following two files (indicated as A and B): FILE A: head 129N.final-test_taxid-120686.txt A00270:507:H3KTJDSX5:4:1105:31747:1736 1187 chr1 205559197 60 144M6S = 205559203 152 GAGCATTTAGGCAAGAGAAAGGAACAAAGGGTATCCAAATTGAAAAACAGGAGTCAAATTGTCCCTTTGCAGACAACAGGATTTTACATATAGAAAAATCTAAAAGATCACACACACACACACACACACACACACACACACACACACAAA FFFFFFFFFFFFFFF:FFFFFFFFFFF:FF:FFFF,FFFFF:FFFF:F:FFFFFF:F:FFFFFF:FFFFFF:FF,FFFFFFFFFFFFFFFFFFFFFF::,FFFF::,FFF,F:FFFFFFFFFFFFFFFF,FFFFFFFFFF:,F,FF,FF: NM:i:0 AS:i:288 nn:i:0 tp:A:P cm:i:18 s1:i:120 s2:i:0 de:f:0 rl:i:86 MQ:i:50 MC:Z:102M4I44M ms:i:4398 A00270:507:H3KTJDSX5:4:1105:31747:1736…

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DNA-bridging by an archaeal histone variant via a unique tetramerisation interface

Chromatin isolation and MNase digestion M. jannaschii DSM 2661 cells were grown in 100 l fermenters in minimal medium containing 0.3 mM K2HPO4, 0.4 mM KH2PO4, 3.6 mM KCl, 0.4 M NaCl, 10 mM NaHCO3, 2.5 mM CaCl2, 38 mM MgCl2, 22 mM NH4Cl, 31 µM Fe(NH4)2(SO4)2, 1 mM C6H9NO6, 1.2 µM MgSO4, 0.4 mM CuSO4, 0.3 µM MnSO4, 36 nM FeSO4, 36 nM CoSO4, 3.5 nM…

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Dealing with transcriptome sequences that are smaller than their respective genes

Dealing with transcriptome sequences that are smaller than their respective genes 1 Hi.I did blastn of a transcriptome that was generated with Trinity against the annotated genome of the organism I work with.Out of the 11007 matches in the blastn results, 2474 are smaller than their respective genes from the…

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Genome-wide promoter responses to CRISPR perturbations of regulators reveal regulatory networks in Escherichia coli

PPTP-seq development and validation PPTP-seq uses plasmid to integrate each CRISPRi-based TF perturbation and each promoter activity reporter into one construct. Each plasmid contains a CRISPRi cassette that constitutively expresses a single guide RNA (sgRNA) to repress a specific TF in the genome19 and a promoter-reporter cassette to measure the…

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FDA Approves Momelotinib for the Treatment of Myelofibrosis and Anemia

Approval for myelofibrosis and anemia marks the first ever inducation for momelotinib in any market.1 The approval comes 4 months after the Prescription Drug User Fee target action date of June 16, 2023. Approval has been granted by the FDA to momelotinib for the treatment of patients with myelofibrosis and…

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FDA Approves Momelotinib to Treat Myelofibrosis With Anemia

Momelotinib (Ojjaara) was granted FDA approval for the treatment of adults with intermediate- or high-risk myelofibrosis, including primary myelofibrosis- or secondary myelofibrosis-related anemia. 1 The regulatory decision is supported by findings from a subpopulation of adult patients with anemia from the phase 3 SIMPLIFY-1 trial (NCT01969838) and the phase 3…

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problem in BIOMOD2

hi, can anyone explain this section, please # myBiomodModelOut <- BIOMOD_Modeling( myBiomodData, models = c('GLM', 'GAM', 'RF', 'SRE', 'MAXENT.Phillips'), models.options = myBiomodOption, NbRunEval=3, DataSplit=70, Prevalence=0.5, VarImport=3, models.eval.meth = c('TSS','ROC'), SaveObj = TRUE, rescal.all.models = TRUE, do.full.models = FALSE, modeling.id = paste('Fagus orientalis',"FirstModeling",sep="")) I tried to train with this scrip that…

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2023-08-28 | NYSE:BMY | Press Release

Results from VALOR-HCM LTE (56 weeks) demonstrated that with longer follow-up, CAMZYOS continued to reduce eligibility for invasive SRT at 56 weeks EXPLORER-LTE data (cumulative analysis up to 120 weeks) showed sustained improvements in LVOT obstruction, symptoms, and NT-proBNP levels in patients with symptomatic obstructive HCM, with no new safety…

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Heatmap ChIP-seq average signal

Heatmap ChIP-seq average signal 1 Hey everybody! I am aiming to generate a heatmap for the average signal of a certain histone mark across all gene coding regions, with TSS as the reference point. I am already aware of how to produce such plots using plotProfile and plotHeatmap from the…

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Bristol-Myers Squibb (BMY) Reports Follow-Up Data from Two Phase 3 Studies of CAMZYOS Demonstrate Consistent and Durable Response

Bristol Myers Squibb (NYSE: BMY) today announced new long-term follow-up results from two Phase 3 studies evaluating CAMZYOS® (mavacamten), a first-in-class cardiac myosin inhibitor, in adult patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Results from the 56-week analysis of the VALOR-HCM long-term extension (LTE) study were presented as a late-breaking…

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list index out of range

ROSE Algorithm: list index out of range 0 I am trying to run the ROSE algorithm created by the young lab. However, i got the problem posted below. Any help is appreciated. Thank you! MAKING TSS COLLECTION Traceback (most recent call last): File “/media/wangxiaohan/software/lib/ROSE-1.3.1/ROSE_geneMapper.py”, line 291, in <modute> main() File…

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RepeatMasker error when trying to generate repeat sequence distribution pie chart (all code and errors provided)

RepeatMasker error when trying to generate repeat sequence distribution pie chart (all code and errors provided) 0 Hi, Any answers would be highly appreciated as I’ve been stuck on this for a while. I analyze epigenetic data and process DMR lists and I’m currently having issues producing a pie chart…

Continue Reading RepeatMasker error when trying to generate repeat sequence distribution pie chart (all code and errors provided)

Interpreting HOMER peak calling score and annotation file

Interpreting HOMER peak calling score and annotation file 0 Hello, I used homer for peak calling and peak annotation for two different conditions. I want to count the differential peaks, which are the peaks that exist in one file but not the other. My question is: Do I simply see…

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Rhox6 regulates the expression of distinct target genes to mediate mouse PGCLC formation and ESC self-renewal | Cell & Bioscience

Overexpression of Rhox6 promotes PGCLC formation To discover potential candidate genes that may be important for the specification of mouse PGCs, we analyzed the transcriptional data of E9.5 PGCs and epiblasts and found that the homeobox family members Rhox6 and Rhox9, as well as the PGC markers Prdm14, Blimp1, Stella…

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Scanning a genomic region for TFBS

I have an answer posted on the Bioinformatics SE that suggests how to use FIMO to scan for TFBS over a genome: bioinformatics.stackexchange.com/a/2491/776 This example uses UCSC to retrieve sequence information, JASPAR for MEME-formatted motif models, and BEDOPS starch to compress the results (which will be sizeable). Once you have…

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Remove peaks on promoters

Remove peaks on promoters 0 Hi, I have a list of peaks in bed format and I would to remove peaks that falls into promoters (+/- 500 bp). I tried with this approach but I’m not sure is it correct. Can anyone confirm it? > peaks GRanges object with 336…

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Boquila: NGS read simulator to eliminate read nucleotide bias in sequence analysis

. 2023 Feb 21;47(2):158-163. doi: 10.55730/1300-0152.2650. eCollection 2023. Affiliations Expand Affiliations 1 Faculty of Engineering and Natural Sciences, Sabancı University, İstanbul, Turkey. 2 TÜBİTAK Research Institute for Fundamental Sciences, Gebze, Turkey. Item in Clipboard Ümit Akköse et al. Turk J Biol. 2023. Show details Display options Display options Format AbstractPubMedPMID ….

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Unusual pattern in heatmap from ChIP-seq

Unusual pattern in heatmap from ChIP-seq 0 Hello! I am plotting some heatmaps for a certain histone mark from a ChIP-seq experiment. I am producing the heatmaps using both computeMatrix and plotHeatmap functions from deeptools. The coordinates regions used for computeMatrix are all coding regions for the mouse genome, sorted…

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How to interpret heatmap using plotheatmap from deeptools?

How to interpret heatmap using plotheatmap from deeptools? 1 The heatmap indicates by color the amount of signal (whatever this is, RPKM, TPM, normalized counts…) in a windows of +/- 3000bp around the TSS which is the center. The more blue the more signal, the more red the less signal….

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Zfp296 knockout enhances chromatin accessibility and induces a unique state of pluripotency in embryonic stem cells

Establishment of Zfp296-deficient ESCs The expression of Zfp296 during ESC differentiation into trophectoderm was examined using the ZHBTc4 ESC line, in which expression of Pou5f1 encoding Oct3/4 can be downregulated by tetracycline20. As shown in Supplementary Fig. 1a, Zfp296 expression rapidly decreased, suggesting that Zfp296 is downstream of Oct3/4. To generate…

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Biomolecules | Free Full-Text | Genome-Wide Acetylation Modification of H3K27ac in Bovine Rumen Cell Following Butyrate Exposure

1. Introduction The digestive tract greatly influences the maintenance of energy requirements in cattle due to its crucial role in digesting and absorbing nutrients. The rumen is an essential organ in the digestive tract for feed efficiency, with relatively high metabolic activities. The digestion of solid-feeding materials generates short-chain fatty…

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Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice | BMC Medicine

The strategy and logic of choosing VRK2 SNPs for genetic analyses We retrieved the summary statistics of VRK2 SNPs in 23andMe, UK Biobank, and PGC2 samples [2, 3], and 256 SNPs region were available in all three GWAS datasets (a total of 246,363 cases and 561,190 controls). An overview about…

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Anatomical and molecular characterization of parvalbumin-cholecystokinin co-expressing inhibitory interneurons: implications for neuropsychiatric conditions

Genetic targeting of CCK+ interneurons restricted by the Dlx5/6 driver line in mouse hippocampus and neocortex CCK isoforms and their preprohormone can be expressed in excitatory neurons in addition to GABAergic interneurons [28]. In order to target CCK+ inhibitory interneurons only, we employed an intersectional genetic strategy by simultaneous co-expression…

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Antisense therapy restores fragile X protein production in human cells

(A) Volcano plot of log2FC of RNA levels (FXS vs TD). Statistically significant changes (P value <0.0002) are shown as blue dots (down-regulated) and red dots (up-regulated). Gray dots refer to unchanged RNAs. (See also Dataset S2). (B) Histograms for TPM values for RNAs that are up or downregulated in…

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Extensive diversity in RNA termination and regulation revealed by transcriptome mapping for the Lyme pathogen Borrelia burgdorferi

Global identification of 3′ ends Initial computational predictions of open reading frames (ORFs) in B. burgdorferi38 overlooked elements such as mRNA boundaries, sRNA genes, and translation initiation from non-canonical start codons. B. burgdorferi transcription start sites (TSSs) and 5′ processed RNA ends were previously detected using 5′RNA-seq37. Here we sought…

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Download | RatGTEx

See the About page for processing and data format specifications. Gene info Gene expression Median TPM per gene per tissue Used for heatmap visualizations log2(count+1) Used to compute allelic fold change Adipose | BLA | Brain | Eye | IL | LHb | Liver | NAcc | NAcc2 | OFC…

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Combination Therapies May Spur Evolution of the Myelofibrosis Treatment Paradigm

JAK inhibitor combination therapies may bolster the efficacy of ruxolitinib (Jakafi) monotherapy in patients with myelofibrosis, although further phase 3 research is necessary to define the roles of these combinations and determine how certain patient subsets may benefit from these and other treatment approaches, according to Prithviraj Bose, MD. The…

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Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos

Timecourse of Hox gene activation in stembryos In gastrulating mouse embryos, Wnt signaling contributes to the formation of the primitive streak from epiblast cells. Likewise, in stembryos cultured as described in ref. 34, a pulse of the Wnt agonist Chiron 48 h after aggregation of mES cells, that is, between 48 h…

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Making use of relative density of genomic features between gene sets

I am looking at a particular genomic feature in two sets of genes: set A is a positive control set, where I know this mark is overall enriched in the genomic DNA of these genes, and set B is a (much larger) negative control set, where it occurs at a…

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Query regarding DNA Methylation Bisulfite Sequencing data analysis

Query regarding DNA Methylation Bisulfite Sequencing data analysis 0 Hi, I am working on DNA Methylation Bisulfite Sequencing data analysis using methylkit and genomation. I am facing an issue while annotating my differentially methylated gene data using annotatewithGeneparts function from genomation. Actually, the number of rows/entries in dist.to.tss sheet and…

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ESHG: German Study Shows Utility of Rapid Whole-Genome Trio Sequencing in Critically Ill Children

GLASGOW – Researchers from Germany have demonstrated the feasibility and utility of rapid whole-genome trio sequencing in critically ill children in the nation’s first multicenter study of its kind. Presenting a poster at the European Society of Human Genetics annual meeting here on Sunday, Bernd Auber, a researcher from Hannover…

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Ruxolitinib Improves Outcomes in Myelofibrosis Regardless of Anemia, Transfusion Status

Image Credit: © Сергей Шиманович -www.stock.adobe.com Findings from a post-hoc analysis of the phase 3 COMFORT-I (NCT00952289) and -II (NCT00934544) revealed that ruxolitinib (Jakafi) improves spleen volume and tumor symptom score (TSS) in patients with myelofibrosis, irrespective of their anemia and transfusion status, according to a presentation at the 2023…

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Y chromosome sequence and epigenomic reconstruction across human populations

Data production Complete Y chromosomes from six different human haplogroups were isolated as previously described17 (Fig. 1a, b). In brief, chromosomes were obtained from lymphoblastoid cell lines (LCLs) used in the 1000 Genomes Project31 (1kgp) and sequenced on the ONT MinION. We also made use of the Y chromosome sorted ONT…

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Expert Advice on CRISPR Design

  The following is an excerpt from an E-book that Twist developed for Genetic Engineering News: The Changing Landscape of CRISPR Screening: A guidebook to the latest CRISPR screening methodologies and technologies. You can download the full E-book here.   Even for seasoned researchers, designing an sgRNA library can be…

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Amplifying gene expression with RNA-targeted therapeutics

RNA-targeted NBTs that are currently being used to upregulate gene expression address both transcriptional and translational mechanisms and can be roughly divided into two groups: (1) NBTs that increase mRNA abundance by enhancing transcription or increasing mRNA stability (Fig. 3) and (2) NBTs that optimize translation (Fig. 4). Strategies in the first…

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Bioconductor – RcisTarget

DOI: 10.18129/B9.bioc.RcisTarget     This package is for version 3.13 of Bioconductor; for the stable, up-to-date release version, see RcisTarget. RcisTarget Identify transcription factor binding motifs enriched on a list of genes or genomic regions Bioconductor version: 3.13 RcisTarget identifies transcription factor binding motifs (TFBS) over-represented on a gene list….

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Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture

We analyzed data from a total of 2,733 participants from the GALA II16 and SAGE17 asthma case–control studies who self-identified as African American (AA; n = 757), Puerto Rican (PR; n = 893), Mexican American (MX; n = 784) or other Latino American (LA; n = 299) (Table 1 and Supplementary Table 1). The median age of the…

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Genes’ fpkm values through cufflink

Hi, I am a newbie to RNA-seq data analysis. I have to identify differentially expressed genes (DEGs) between human and chimpanzee in a tissue type. I have comparable RNA-seq experiment data (reads/fastq) for the two species. Each species has 2 biological replicates(each with three technical replicates) so six runs per…

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PhaeoEpiView: an epigenome browser of the newly assembled genome of the model diatom Phaeodactylum tricornutum

Despite being an established model, the genome and annotation of P. tricornutum are not concordant and the existing epigenetic resources generated so far lack a well-defined framework for accurate and user friendly utilization. To address this limitation, we sought to establish a coherent resource rendering the multiple genomic and epigenomic…

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A guide through the genome of crops

BZR1 regulatory network in maize and Arabidopsis. a Distribution of ZmBZR1 binding around transcribed genes. Frequency of ZmBZR1 binding peaks up to 10 kb up- or downstream of TSS or TTS and intra-genic, respectively. b ChIP-seq identified ZmBZR1 binding in proximity of putative targets repressed (BR6ox2/BRD1), induced (IAA19) or not controlled…

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Quantitative DNA-RNA Immunoprecipitation Sequencing with Spike-Ins – PubMed DNA:RNA ImmunoPrecipitation and high-throughput sequencing.

doi: 10.1007/978-1-0716-2477-7_26. Memberships Expand Connections 1 Department about Chemical and Systems Biology, Stanford University, Stand-ford, CANCER, USA. [email protected] 2 Department of Chemical and Systems Nature, Stanford University, Stanford, CA, USA. [email protected] Freely PMC article Item in Clipboard Magdalena P Crossley et aluminium. Methods Mol Bil. 2022. Free PMC books Show details…

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Mesa Highlights JAK Inhibition for the Treatment of Myelofibrosis

JAK inhibitors have paved the way and improved clinical outcomes for patients with myeloproliferative neoplasms over the past decade. Not only have these agents shown significant improvements in efficacy outcomes, but they have demonstrated favorable safety profiles in this patient population. Currently, 3 JAK inhibitors are approved for patients with…

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best annotation approach for peaks

hi, I have a question or suggestion for you all. I have some peaks and I would to annotate them. My goal is to extend the annotation 10000 upstream from the start of the gene and 10000 downstream from the end of the gene body. So I don’t want to…

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The beginning is the end

image: Example of a gene that contains two possible start sites (TSS), and two possible end sites (TES). Black boxes in the gene model show sequences that will be translated into protein. With conventional short-read mRNA sequencing, in which signal represents the accumulation of reads, it is not possible to distinguish…

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How promoters predefine where genes end

Example of a gene that contains two possible start sites (TSS), and two possible end sites (TES). Black boxes in the gene model show sequences that will be translated into protein. With conventional short-read mRNA sequencing, in which signal represents the accumulation of reads, it is not possible to distinguish…

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By Transcript or by Gene? Code Validation Help Needed!

Hey everyone, I’m currently working on annotating TSS (Transcription Start Site) information, and I have come across a dilemma: should I annotate TSS by transcript or by gene? I would really appreciate your insights and opinions on this matter. On a related note, I have been trying to implement a…

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python – Error while running computeMatrix command in Deeptools

I am trying to get computeMatrix for bigwig file in specific genomic region using deeptools.Below is the code I am using computeMatrix reference-point –referencePoint TSS \ -b 1000 -a 1000 \ -R ~/Desktop/ATAC/ATAC/Inducible_elements_Greenberg.bed \ -S ~/Desktop/ATAC/Control.mRp.clN.bigWig \ –skipZeros \ -o ~/Desktop/ATAC/matrix_controlmRPATACBasalcomputematrix.gz \ But I get the following error File “/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/numpy/__init__.py”,…

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Mobile element variation contributes to population-specific genome diversification, gene regulation and disease risk

Development and benchmarking of MEGAnE Accurate variant genotyping is required for statistical genetics. To enable both discovery and accurate MEV genotyping from genomes studied using short reads, we developed a new bioinformatic tool, mobile element genotype analysis environment (MEGAnE; Supplementary Note). Compared to SVs resolved by long reads, MEGAnE discovers…

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MANIFEST-2 Study of Pelabresib Plus Ruxolitinib Completes Enrollment in Myelofibrosis

Enrollment to the phase 3 MANIFEST-2 trial (NCT04603495), which is examining the safety and efficacy of pelabresib plus ruxolitinib (Jakafi) vs ruxolitinib alone in patients with JAK inhibitor–naïve myelofibrosis, has completed and topline findings are anticipated by the end of 2023.1 The multicenter, double-blind, placebo-controlled, trial enrolled patients with primary,…

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How to find coordinates of TSS from 5pUTR and TTS from 3pUTR in transcriptome/ mRNA ?

How to find coordinates of TSS from 5pUTR and TTS from 3pUTR in transcriptome/ mRNA ? 0 Hello Researchers Can you please tell me just the correct coordinates of TSS(1kb) from 5pUTR + & – strand and TTS(1kb) from 3pUTR + & – strand of transcriptome/ mRNA? I only have…

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rules for choosing guides for multiplex CRISPRa an…

I was wondering if anybody has information on how to choose guides for optimal gene activation/repression using multiplex CRISPR/Cas9s with only two guides? I have tried different combinations e.g. two guides with average activity v.s. one poor guide plus an average guide and got mixed results. Sometimes the latter outperformed…

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Retrieve Promoter Sequences by GeneID

Retrieve Promoter Sequences by GeneID 0 Hello! I want to retrieve promoter sequences starting from a list of Gene_ID, i had try to used RSAT-retrieve sequence, but the problem is that they retrieve the sequence from the start codon or the stop codon, but i want retrieve the sequence 1500bp…

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Annotating and prioritizing human non-coding variants with RegulomeDB v.2

Nearly 90% of the disease risk-associated variants identified by genome-wide association studies are in non-coding regions of the genome. The annotations obtained by analyzing functional genomics assays can provide additional information to pinpoint causal variants, which are often not the lead variants identified from association studies. However, the lack of…

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