[ASAP] A Multimodal SIMS/MALDI Mass Spectrometry Imaging Source with Secondary Electron Imaging Capabilities for Use with timsTOF Instruments

Journal of The American Society for Mass Spectrometry

Journal of the American Society for Mass Spectrometry: Latest Articles (ACS Publications)

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[ASAP] A Multimodal SIMS/MALDI Mass Spectrometry Imaging Source with Secondary Electron Imaging Capabilities for Use with timsTOF Instruments

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Journal of the American Society for Mass Spectrometry
DOI: 10.1021/jasms.2c00381

Kasper Krijnen, Joel D. Keelor, Sebastian Böhm, Shane R. Ellis, Claus Köster, Jens Höhndorf, Ron M. A. Heeren, and Ian G. M. Anthony
March 9, 2023
http://dx.doi.org/10.1021/jasms.2c00381

[ASAP] IP-LC-MSMS Enables Identification of Three Tau O‑GlcNAcylation Sites as O‑GlcNAcase Inhibition Pharmacodynamic Readout in Transgenic Mice Overexpressing Human Tau

Journal of Proteome Research

Journal of Proteome Research: Latest Articles (ACS Publications)

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[ASAP] IP-LC-MSMS Enables Identification of Three Tau O‑GlcNAcylation Sites as O‑GlcNAcase Inhibition Pharmacodynamic Readout in Transgenic Mice Overexpressing Human Tau

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Journal of Proteome Research
DOI: 10.1021/acs.jproteome.2c00822

Sebastiaan Bijttebier, Dina Rodrigues Martins, Liesbeth Mertens, Karolien Grauwen, Wouter Bruinzeel, Roland Willems, José Manuel Bartolomé-Nebreda, Clara Theunis, Alexis Bretteville, Andreas Ebneth, and Lieve Dillen
March 8, 2023
http://dx.doi.org/10.1021/acs.jproteome.2c00822

A multiscale functional map of somatic mutations in cancer integrating protein structure and network topology

BioRxiv

bioRxiv Subject Collection: Systems Biology
This feed contains articles for bioRxiv Subject Collection "Systems Biology"

A multiscale functional map of somatic mutations in cancer integrating protein structure and network topology

A major goal of cancer biology is to understand the mechanisms underlying tumorigenesis driven by somatically acquired mutations. Existing computational approaches focus on either scoring the pathogenicity of mutations or characterizing their effects at specific scales. Here, we established a unified computational framework, NetFlow3D, that systematically maps the multiscale mechanistic effects of somatic mutations in cancer. The establishment of NetFlow3D hinges upon the Human Protein Structurome, a complete repository we first compiled that incorporates the 3D structures of every single protein as well as the binding interfaces for all known PPIs in humans. The vast majority of 3D structural information was resolved by recent deep learning algorithms. By applying NetFlow3D to 415,017 somatic protein-altering mutations in 5,950 TCGA tumors across 19 cancer types, we identified 1,656 intra- and 3,343 inter-protein 3D clusters of mutations throughout the Human Protein Structurome, of which ~50% would not have been found if using only experimentally-determined protein structures. These 3D clusters have converging effects on 377 cellular subnetworks. Compared to canonical PPI network analyses, NetFlow3D achieved a 5.5-fold higher statistical power for identifying significantly dysregulated subnetworks. The majority of identified subnetworks were previously obscured by the overwhelming background noise of non-clustered passenger mutations, including portions of non-canonical PRC1, mediator complex, MCM2-7 complex, neddylation of cullins, complement system, TRiC, etc. NetFlow3D and our pan-cancer results can be accessed from http://netflow3d.yulab.org. This work shows that mapping how individual mutations act across scales requires the integration of their local spatial organization on protein structures and their global topological organization in the PPI network.
Zhang, Y., Leung, A. K., Qiu, T., Li, L., Zhang, J., Wierbowski, S., Booth, J., Yu, H.
March 8, 2023
http://biorxiv.org/cgi/content/short/2023.03.06.531441v1?rss=1

Development and validation of a method for analyzing the sialylated glycopeptides of recombinant erythropoietin in urine using LC–HRMS

Nature Mass Spectrometry

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Development and validation of a method for analyzing the sialylated glycopeptides of recombinant erythropoietin in urine using LC–HRMS

March 8, 2023
https://www.nature.com/articles/s41598-023-31030-y

[ASAP] Comparison of Pairwise Venous and Fingertip Plasma Using Quantitative Proteomics Based on Data-Independent Acquisition

Journal of Proteome Research

Journal of Proteome Research: Latest Articles (ACS Publications)

latest articles published in Journal of Proteome Research

[ASAP] Comparison of Pairwise Venous and Fingertip Plasma Using Quantitative Proteomics Based on Data-Independent Acquisition

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Journal of Proteome Research
DOI: 10.1021/acs.jproteome.3c00081

Ganfei Xu, Jiacheng Lv, Mingjing Huang, Lingli Zhu, Subei Tan, and Chen Ding
March 7, 2023
http://dx.doi.org/10.1021/acs.jproteome.3c00081

[ASAP] Identification, Measurement, and Assessment of the Clinical Utility of Human Pancreatic Polypeptide by Liquid Chromatography–Tandem Mass Spectrometry

Journal of Proteome Research

Journal of Proteome Research: Latest Articles (ACS Publications)

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[ASAP] Identification, Measurement, and Assessment of the Clinical Utility of Human Pancreatic Polypeptide by Liquid Chromatography–Tandem Mass Spectrometry

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Journal of Proteome Research
DOI: 10.1021/acs.jproteome.2c00829

Anthony Maus, Erica M. Fatica, Robert Taylor, Bethany J. Larson, Alicia Algeciras-Schimnich, Ravinder J. Singh, and Stefan K. Grebe
March 7, 2023
http://dx.doi.org/10.1021/acs.jproteome.2c00829

Proteomic analysis reveals CAAP1 negatively correlates with platinum resistance in ovarian cancer

Journal of Proteomics

ScienceDirect Publication: Journal of Proteomics

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Proteomic analysis reveals CAAP1 negatively correlates with platinum resistance in ovarian cancer

Publication date: 15 April 2023

Source: Journal of Proteomics, Volume 277

Author(s): Maowei Ni, Jie Zhou, Wangang Gong, Ruibin Jiang, Xia Li, Wumin Dai, Zhuomin Yin, Zhongbo Chen, Zhiguo Zheng, Jianqing Zhu

March 7, 2023
https://www.sciencedirect.com/science/article/pii/S1874391923000532?dgcid=rss_sd_all

Age-stratified proteomic characteristics and identification of promising precise clinical treatment targets of colorectal cancer

Journal of Proteomics

ScienceDirect Publication: Journal of Proteomics

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Age-stratified proteomic characteristics and identification of promising precise clinical treatment targets of colorectal cancer

Publication date: 15 April 2023

Source: Journal of Proteomics, Volume 277

Author(s): Qianqian Wang, Yuanchen Zhou, Geyujia Zhou, Geng Qin, Chang Tan, Tengfei Yin, Dongyan Zhao, Shukun Yao

March 7, 2023
https://www.sciencedirect.com/science/article/pii/S1874391923000520?dgcid=rss_sd_all

[ASAP] Multistage Ion Mobility Spectrometry Combined with Infrared Spectroscopy for Glycan Analysis

Journal of The American Society for Mass Spectrometry

Journal of the American Society for Mass Spectrometry: Latest Articles (ACS Publications)

latest articles published in Journal of the American Society for Mass Spectrometry

[ASAP] Multistage Ion Mobility Spectrometry Combined with Infrared Spectroscopy for Glycan Analysis

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Journal of the American Society for Mass Spectrometry
DOI: 10.1021/jasms.2c00361

Priyanka Bansal, Ahmed Ben Faleh, Stephan Warnke, and Thomas R. Rizzo
March 7, 2023
http://dx.doi.org/10.1021/jasms.2c00361

Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control

Rapid Communications in Mass Spectrometry

Wiley: Rapid Communications in Mass Spectrometry: Table of Contents

Table of Contents for Rapid Communications in Mass Spectrometry. List of articles from both the latest and EarlyView issues.

Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control

Rationale

Since 2010, there has been an increasing number of adverse analytical findings related to selective androgen receptor modulators (SARMs) in competitive sports. It emphasizes the importance of comprehensive doping control analytical procedures that are capable of detecting SARM misuse.

Methods

In this study, it is described how LY2452473, a SARM, was metabolized in thoroughbred horses after a single-dose oral administration and in vitro with equine liver microsome preparations. An investigation of the metabolism of LY2452473 in horses’ urine, plasma, and hair matrices was carried out during the study. The plausible structures of the detected metabolites were postulated using high-performance liquid chromatography-high resolution mass spectrometry.

Results

Under the experimental conditions 15 metabolites (12 phase I and three conjugates of phase I) were detected (M1–M15). The major phase I metabolites identified were formed by hydroxylation. Side-chain dissociated and methylated metabolites were also detected. In phase II, the glucuronic acid and sulfonic acid conjugates of hydroxy LY2452473 were detected as the major metabolites. In vitro analysis has confirmed the presence of all metabolites found in vivo except for the methylated analogs M11 and M12. A peak concentration of LY2452473 (0.5 pg/mg) in proximal hair segments was achieved 4 weeks after administration, according to hair analysis.

Conclusions

Data obtained will aid in identifying LY2452473 and related substances faster. Furthermore, the results will assist in checking for the illegal use of these substances in competitive sports.

Tajudheen K. Karatt,
M. Anwar Sathiq,
Saraswathy Laya,
Abdul Khader Karakka Kal,
Michael Benedict Subhahar,
Muhammed Ajeebsanu M.P,
Moses Philip,
Fatma Mohammed Graiban,
Marina Rodriguez Caveney
March 7, 2023
https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/rcm.9491?af=R

Glutathione conjugation of nitrogen mustards: In vitro study

Rapid Communications in Mass Spectrometry

Wiley: Rapid Communications in Mass Spectrometry: Table of Contents

Table of Contents for Rapid Communications in Mass Spectrometry. List of articles from both the latest and EarlyView issues.

Glutathione conjugation of nitrogen mustards: In vitro study

Rationale

This paper describes an in vitro study designed to identify metabolic biomarkers resulting from the conjugation of nitrogen mustards (NMs) with glutathione (GSH). The method developed is essential in providing evidence in the event of NM exposure in biomedical samples.

Methods

The mass spectral characterization of the proposed NMs–GSH conjugates was performed with liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). The final reaction mixtures were analysed in positive electrospray ionisation (ESI) at different incubation times.

Results

This study identified three types of conjugates in addition to ethanolamines, the hydrolysis products of NMs. Monoglutathionyl, diglutathionyl and phosphorylated conjugates were produced for each of the NMs, bis(2-chloroethyl)ethylamine (HN1), bis(2-chloroethyl)methylamine (HN2) and tris(2-chloroethyl)amine (HN3). The monoglutathionyl conjugates consisted of HN1-GSH, HN2-GSH and HN3-GSH. The spontaneous and primary conjugates of diglutathionyl were HN1-GSH2, HN2-GSH2 and HN3-GSH2. These included phosphorylated conjugates, namely HN1-GSH-PO4, HN2-GSH-PO4 and HN3-GSH-PO4, as might have formed due to hydrolysis in phosphate buffer.

Conclusions

The mass spectral data of all conjugates formed in the presence of all NMs and GSH are reported in this study. These GSH metabolites can be used to confirm NMs toxicity in biological samples such as urine.

Nurhazlina Hamzah,
Matti Kjellberg,
Paula Vanninen
March 7, 2023
https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/rcm.9495?af=R

An improved strategy for identification and annotation of easily in‐sourced dissociation diterpene lactones from plant natural products: Taking Andrographis paniculata (Burm. f.) as an example

Rapid Communications in Mass Spectrometry

Wiley: Rapid Communications in Mass Spectrometry: Table of Contents

Table of Contents for Rapid Communications in Mass Spectrometry. List of articles from both the latest and EarlyView issues.

An improved strategy for identification and annotation of easily in‐sourced dissociation diterpene lactones from plant natural products: Taking Andrographis paniculata (Burm. f.) as an example

Rationale

Diterpene lactones (DL) in Andrographis paniculata (AP) are known as “natural antibiotics” for their excellent antibacterial activity. During mass spectrometry (MS) analysis, the hydroxyl groups in the AP DL skeleton are prone to neutral loss of H2O, producing high in-source fragment peaks and affecting the characterization of these components.

Methods

Mass tags were applied during the MS data acquisition step, and special adduct ion form was used to guide the data processing and characterization steps. Besides, the total number of characterized AP DLs significantly increased when combining the number of neutrally lost H2O from AP DLs, incorporating information on the diagnostic ions, and adopting molecular networks generated with the Global Natural Products Social Molecular Networking database.

Results

Ninety-nine DLs, comprising 6 monohydroxyl groups, 20 dihydroxyl groups, 27 trihydroxy groups, and 46 DLs with more than 3 hydroxyl groups, were characterized from AP. In addition, based on the characteristic fragments in the product ions (C3H4, Δm/z = 40.03 Da), it could be assumed that 90 DLs had the C19-OH structure among the identified DLs. The current study provides a new approach for collecting, processing, and characterizing MS analysis of natural DLs prone to in-source fragmentation.

Conclusions

MS characterization of AP DLs was significantly improved, and many potential new compounds were identified in AP. This characterization provides new methods for the purification and identification of AP DLs.

Xingdong Wu,
Hongwei Ding,
Zijia Zhang,
Man Zheng,
Hui Ni,
Zhiyun Huang,
Wenyong Wu,
Huali Long,
Yang Zhou,
Feifei Li,
Min Lei,
Jinjun Hou,
Wanying Wu,
Dean Guo
March 7, 2023
https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/rcm.9483?af=R

Assessment of the accuracy of the 17O correction algorithm used in δ13C determinations by CO2 mass spectrometry

Rapid Communications in Mass Spectrometry

Wiley: Rapid Communications in Mass Spectrometry: Table of Contents

Table of Contents for Rapid Communications in Mass Spectrometry. List of articles from both the latest and EarlyView issues.

Assessment of the accuracy of the 17O correction algorithm used in δ13C determinations by CO2 mass spectrometry

Rationale

High-accuracy δ
13C values are required for observations of greenhouse gases CO2 and methane, and, consequently, for international reference materials (RMs). Recently, another application, clumped isotope geothermometry of natural carbonates, has demonstrated the requirement for high-accuracy δ
13C values. δ
13C determinations by mass spectrometry use an 17O isobaric correction on m/z 45, where 17O abundance is calculated from the measured 18O with the 17O–18O relationship assumed with λ = 0.528. This relationship is the key assumption of the algorithm proposed in 2003 and accepted by IUPAC in 2010. However, to date, this relationship and potential δ
13C biases have not been verified using 17O measurements.

Methods

To verify the 17O correction and to estimate potential δ
13C biases, we compile measured 17O data for carbonate RMs, for a range of natural carbonates that are typically analyzed in clumped isotope geothermometry and for CO2 in isotope equilibrium with natural waters including plants and biota. δ
13C biases are calculated based on 17O deviation from the 17O–18O relationship assumed in the 17O correction.

Results

To estimate δ
13C biases accurately, the VPDB-CO2 framework for expressing 17O excess is defined and linked to the δ
13C scale definition. δ
13C biases estimated for carbonate RMs are found within ±0.004‰; the biases estimated for natural carbonates and CO2 in equilibrium with natural waters are mostly within ±0.010‰ (bidirectional distribution around zero). In all cases, the estimated biases are found within the best instrumental uncertainty of modern isotope ratio mass spectrometry (IRMS) (around ±0.014‰, k = 2).

Conclusions

For the first time, high accuracy of δ
13C data obtained by CO2 mass spectrometry using the 17O correction with fixed λ = 0.528 has been demonstrated using measured 17O data. δ
13C biases estimated are within the best IRMS precision (±0.014‰, k = 2) and can be neglected in most practical applications. To obtain high-quality δ
13C data, it is strictly necessary that all data are treated on the VPDB-CO2 scale.

Sergey Assonov
March 7, 2023
https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/rcm.9490?af=R

Ultra‐low Current Electrospray Ionization of Chloroform Solution for the Analysis of Perfluorinated Sulfonic Acids

Rapid Communications in Mass Spectrometry

Wiley: Rapid Communications in Mass Spectrometry: Table of Contents

Table of Contents for Rapid Communications in Mass Spectrometry. List of articles from both the latest and EarlyView issues.

Ultra‐low Current Electrospray Ionization of Chloroform Solution for the Analysis of Perfluorinated Sulfonic Acids

Rationale

Femtoamp and picoamp electrospray ionization characteristics of a non-polar solvent were explored. The direct ESI-MS analysis of chloroform extract solution enabled rapid analysis of perfluorinated sulfonic acid (PFS) analytes in drinking water.

Methods

Neat chloroform solvent and extracts were directly used in a typical wire-in ESI setup using micrometer emitter tips. Ionization currents were measured with femtoamp sensitivity while ramping the spray voltage from 0 to -5000 V. Methanol was used to illustrate the characteristics of spraying chloroform. The effects of spray voltage and inlet temperature were studied. A liquid-liquid extraction workflow was developed to analyze PFOS in drinking water using an ion trap mass spectrometer.

Results

The ionization onset of chloroform solution was 41 ± 17 fA at 300 V. The ionization current gradually increased with voltage while remaining below 100 pA when using voltages up to -5000 V. The ion signal of PFOS was significantly enhanced to improve the limit of detection (LoD) to 25 ppt in chloroform. Coupled with a liquid-liquid extraction workflow, LoD of 0.38-5.1 ppt, and a quantitation range of 5-400 ppt were achieved for perfluorinated sulfonic compounds in 1 mL water samples.

Conclusions

Femtoamp and picoamp modes expand the solvent compatibility range of electrospray ionization and can enable quantitative analysis in ppt concentrations.

Taoqing Wang,
Huishan Li,
Nicholas Allen,
Ian Ferraro,
Anyin Li
March 7, 2023
https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/rcm.9501?af=R

A gas phase fractionation acquisition scheme integrating ion mobility for rapid diaPASEF library generation

Proteomics (Wiley)

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A gas phase fractionation acquisition scheme integrating ion mobility for rapid diaPASEF library generation

Abstract

Data independent acquisition (DIA/SWATH) MS is a primary strategy in quantitative proteomics. diaPASEF is a recent adaptation using trapped ion mobility spectrometry (TIMS) to improve selectivity/sensitivity. Complex DIA spectra are typically analyzed with reference to spectral libraries. The best-established method for generating libraries uses offline fractionation to increase depth of coverage. More recently strategies for spectral library generation based on gas phase fractionation (GPF), where a representative sample is injected serially using narrow DIA windows that cover different mass ranges of the complete precursor space, have been introduced that performed comparably to deep offline fractionation-based libraries. We investigated whether an analogous GPF-based approach that accounts for the ion mobility (IM) dimension is useful for the analysis of diaPASEF data. We developed a rapid library generation approach using an IM-GPF acquisition scheme in the m/z vs 1/K0 space requiring 7 injections of a representative sample and compared this with libraries generated by direct deconvolution-based analysis of diaPASEF data or by deep offline fractionation. We found that library generation by IM-GPF outperformed direct library generation from diaPASEF and had performance approaching that of the deep library. This establishes the IM-GPF scheme as a pragmatic approach to rapid library generation for analysis of diaPASEF data.

This article is protected by copyright. All rights reserved

Jack Penny,
Mohammad Arefian,
Gunnar N. Schroeder,
José A. Bengoechea,
Ben C. Collins
March 7, 2023
https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/pmic.202200038?af=R

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with impaired kidney function.

BioRxiv

bioRxiv Subject Collection: Systems Biology
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Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with impaired kidney function.

Objective: Bowel movement frequency (BMF) variation has been linked to changes in the composition of the human gut microbiome and to many chronic conditions, like metabolic disorders, neurodegenerative diseases, chronic kidney disease (CKD), and other intestinal pathologies like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Slow intestinal transit times (constipation) are thought to lead to compromised intestinal barrier integrity and a switch from saccharolytic to proteolytic fermentation within the microbiota, giving rise to microbially-derived toxins that may make their way into circulation and cause damage to organ systems. However, these phenomena have not been characterized in generally-healthy populations, and the connections between microbial metabolism and the early-stage development and progression of chronic disease remain underexplored. Design: Here, we examine the phenotypic impact of BMF variation across a cohort of over 2,000 generally-healthy, community dwelling adults with detailed clinical, lifestyle, and multi-omic data. Results: We show significant differences in key blood plasma metabolites, proteins, chemistries, gut bacterial genera, and lifestyle factors across BMF groups that have been linked, in particular, to inflammation and CKD severity and progression. Discussion: In addition to dissecting BMF-related heterogeneity in blood metabolites, proteins, and the gut microbiome, we identify self-reported diet, lifestyle, and psychological factors associated with BMF variation, which suggest several potential strategies for mitigating constipation and diarrhea. Overall, this work highlights the potential for managing BMF to prevent disease.
Johnson, J. P., Diener, C., Levine, A. E., Wilmanski, T., Suskind, D. L., Ralevski, A., Hadlock, J., Magis, A. T., Hood, L., Rappaport, N., Gibbons, S. M.
March 7, 2023
http://biorxiv.org/cgi/content/short/2023.03.04.531100v1?rss=1

Beyond the Genetic Code: A Tissue Code?

BioRxiv

bioRxiv Subject Collection: Systems Biology
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Beyond the Genetic Code: A Tissue Code?

The genetic code determines how the precise amino acid sequence of proteins is specified by genomic information in cells. But what specifies the precise histologic organization of cells in plant and animal tissues is unclear. We now hypothesize that another code, the tissue code, exists at an even higher level of complexity which determines how tissue organization is dynamically maintained. Accordingly, we modeled spatial and temporal asymmetries of cell division and established that five simple mathematical laws (the tissue code) convey a set of biological rules that maintain the specific organization and continuous self-renewal dynamics of cells in tissues. These laws might even help us understand wound healing, and how tissue disorganization leads to birth defects and tissue pathology like cancer.
Boman, B. M., Dinh, T.-N., Decker, K., Emerick, B., Modarai, S., Opdenaker, L., Fields, J. Z., Raymond, C., Schleiniger, G.
March 7, 2023
http://biorxiv.org/cgi/content/short/2023.03.05.531161v1?rss=1

[ASAP] Large-Scale Profiling of Unexpected Tryptic Cleaved Sites at Ubiquitinated Lysines

Journal of Proteome Research

Journal of Proteome Research: Latest Articles (ACS Publications)

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[ASAP] Large-Scale Profiling of Unexpected Tryptic Cleaved Sites at Ubiquitinated Lysines

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Journal of Proteome Research
DOI: 10.1021/acs.jproteome.2c00748

Zhen Sun, Weidi Xiao, Naikang Li, Lei Chang, Ping Xu, and Yanchang Li
March 6, 2023
http://dx.doi.org/10.1021/acs.jproteome.2c00748

Transcription factor interactions explain the context-dependent activity of CRX binding sites

BioRxiv

bioRxiv Subject Collection: Systems Biology
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Transcription factor interactions explain the context-dependent activity of CRX binding sites

The effects of transcription factor binding sites (TFBSs) on the activity of a cis-regulatory element (CRE) depend on the local sequence context. In rod photoreceptors, binding sites for the transcription factor (TF) Cone-rod homeobox (CRX) occur in both enhancers and silencers, but the sequence context that determines whether CRX binding sites contribute to activation or repression of transcription is not understood. To investigate the context-dependent activity of CRX sites, we fit neural network-based models to the activities of synthetic CREs composed of photoreceptor TFBSs. The models revealed that CRX binding sites consistently make positive, independent contributions to CRE activity, while negative homotypic interactions between sites cause CREs composed of multiple CRX sites to function as silencers. The effects of negative homotypic interactions can be overcome by the presence of other TFBSs that either interact cooperatively with CRX sites or make independent positive contributions to activity. The context-dependent activity of CRX sites is thus determined by the balance between positive heterotypic interactions, independent contributions of TFBSs, and negative homotypic interactions. Our findings explain observed patterns of activity among genomic CRX-bound enhancers and silencers, and suggest that enhancers may require diverse TFBSs to overcome negative homotypic interactions between TFBSs.
Loell, K. J., Friedman, R. Z., Myers, C. A., Corbo, J. C., Cohen, B. A., White, M. A.
March 6, 2023
http://biorxiv.org/cgi/content/short/2023.03.05.531194v1?rss=1