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Key Publications

Transcription feedback dynamics in the wake of cytoplasmic mRNA degradation shutdown

A Chappleboim, D Joseph-Strauss, O Gershon, N Friedman

Nucleic Acids Research 50 (10), 5864-5880

Conserved degronome features governing quality control-associated proteolysis

B Mashahreh, S Armony, KE Johansson, A Chappleboim, N Friedman, ...

bioRxiv

Subtyping of Small Cell Lung Cancer using plasma cell-free nucleosomes

G Fialkoff, N Takahashi, I Sharkia, J Gutin, L Pongor, A Rajan, S Nichols, ...

bioRxiv

Early sample tagging and pooling enables simultaneous SARS-CoV-2 detection and variant sequencing

A Chappleboim, D Joseph-Strauss, A Rahat, I Sharkia, M Adam, ...

Science Translational Medicine 13 (618), eabj2266

NovoSpaRc: flexible spatial reconstruction of single-cell gene expression with optimal transport

N Moriel, E Senel, N Friedman, N Rajewsky, N Karaiskos, M Nitzan

Nature Protocols 16 (9), 4177-4200

ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin

R Sadeh, I Sharkia, G Fialkoff, A Rahat, J Gutin, A Chappleboim, M Nitzan, ...

NATURE BIOTECHNOLOGY

 

Selective flexible packaging pathways of the segmented genome of influenza A virus

I Haralampiev, S Prisner, M Nitzan, M Schade, F Jolmes, M Schreiber, ...

Nature communications 11 (1), 1-13

 

Flexibility and constraint in preimplantation gene regulation in mouse

CC Conine, M Krykbaeva, L Song, RC Brewster, N Friedman, OJ Rando

bioRxiv

 

Deciphering eukaryotic gene-regulatory logic with 100 million random promoters

CG de Boer, ED Vaishnav, R Sadeh, EL Abeyta, N Friedman, A Regev

Nature biotechnology 38 (1), 56-65

 

Gene expression cartography

M Nitzan, N Karaiskos, N Friedman, N Rajewsky

Nature 576 (7785), 132-137

 

Genetic screen of the yeast environmental stress response dynamics uncovers distinct regulatory phases

J Gutin, D Joseph‐Strauss, A Sadeh, E Shalom, N Friedman

Molecular systems biology 15 (8), e8939

 

Dynamics of chromatin and transcription during transient depletion of the RSC chromatin remodeling complex

A Klein-Brill, D Joseph-Strauss, A Appleboim, N Friedman

Cell reports 26 (1), 279-292. e5

 

Fine-resolution mapping of TF binding and chromatin interactions

J Gutin, R Sadeh, N Bodenheimer, D Joseph-Strauss, A Klein-Brill, ...

Cell reports 22 (10), 2797-2807

 

Temporal profiling of redox-dependent heterogeneity in single cells

M Radzinski, R Fassler, O Yogev, W Breuer, N Shai, J Gutin, S Ilyas, ...

Elife 7

 

A synthetic biology approach to probing nucleosome symmetry

Y Ichikawa, CF Connelly, A Appleboim, TCR Miller, H Jacobi, NA Abshiru, ...

elife 6, e28836

 

Perturb-Seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens

A Dixit, O Parnas, B Li, J Chen, CP Fulco, L Jerby-Arnon, ND Marjanovic, ...

cell 167 (7), 1853-1866. e17

 

Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection

G Levy, N Habib, MA Guzzardi, D Kitsberg, D Bomze, E Ezra, BE Uygun, ...

Nature chemical biology 12 (12), 1037-1045

 

Mapping the landscape of a eukaryotic degronome

Y Geffen, A Appleboim, RG Gardner, N Friedman, R Sadeh, T Ravid

Molecular cell 63 (6), 1055-1065

 

Elucidating combinatorial chromatin states at single-nucleosome resolution

R Sadeh, R Launer-Wachs, H Wandel, A Rahat, N Friedman

Molecular cell 63 (6), 1080-1088

332016

Early sample tagging and pooling enables simultaneous SARS-CoV-2 detection and variant sequencing

September 20, 2021

Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic tests have relied on RNA extraction followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays. Whereas automation improved logistics and different pooling strategies increased testing capacity, highly multiplexed next-generation sequencing (NGS) diagnostics remain a largely untapped resource. NGS tests have the potential to markedly increase throughput while providing crucial SARS-CoV-2 variant information. Current NGS-based detection and genotyping assays for SARS-CoV-2 are costly, mostly due to parallel sample processing through multiple steps. Here, we have established ApharSeq, in which samples are barcoded in the lysis buffer and pooled before reverse transcription. We validated this assay by applying ApharSeq to more than 500 clinical samples from the Clinical Virology Laboratory at Hadassah hospital in a robotic workflow. The assay was linear across five orders of magnitude, and the limit of detection was Ct 33 (~1000 copies/ml, 95% sensitivity) with >99.5% specificity. ApharSeq provided targeted high-confidence genotype information due to unique molecular identifiers incorporated into this method. Because of early pooling, we were able to estimate a 10- to 100-fold reduction in labor, automated liquid handling, and reagent requirements in high-throughput settings compared to current testing methods. The protocol can be tailored to assay other host or pathogen RNA targets simultaneously. These results suggest that ApharSeq can be a promising tool for current and future mass diagnostic challenges.

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