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Article ; Online: What fraction of cellular DNA turnover becomes cfDNA?

Sender, Ron / Noor, Elad / Milo, Ron / Dor, Yuval

2024 Volume 12

Abstract: Cell-free DNA (cfDNA) tests use small amounts of DNA in the bloodstream as biomarkers. While it is thought that cfDNA is largely released by dying cells, the proportion of dying cells' DNA that reaches the bloodstream is unknown. Here, we integrate ... ...

Abstract	Cell-free DNA (cfDNA) tests use small amounts of DNA in the bloodstream as biomarkers. While it is thought that cfDNA is largely released by dying cells, the proportion of dying cells' DNA that reaches the bloodstream is unknown. Here, we integrate estimates of cellular turnover rates to calculate the expected amount of cfDNA. By comparing this to the actual amount of cell type-specific cfDNA, we estimate the proportion of DNA reaching plasma as cfDNA. We demonstrate that <10% of the DNA from dying cells is detectable in plasma, and the ratios of measured to expected cfDNA levels vary a thousand-fold among cell types, often reaching well below 0.1%. The analysis suggests that local clearance, presumably via phagocytosis, takes up most of the dying cells' DNA. Insights into the underlying mechanism may help to understand the physiological significance of cfDNA and improve the sensitivity of liquid biopsies.
MeSH term(s)	Cell-Free Nucleic Acids ; Phagocytosis ; Liquid Biopsy ; DNA ; Kinetics
Chemical Substances	Cell-Free Nucleic Acids ; DNA (9007-49-2)
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.89321
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The distribution of cellular turnover in the human body.

Sender, Ron / Milo, Ron

Nature medicine

2021 Volume 27, Issue 1, Page(s) 45–48

Abstract: We integrated ubiquity, mass and lifespan of all major cell types to achieve a comprehensive quantitative description of cellular turnover. We found a total cellular mass turnover of 80 ± 20 grams per day, dominated by blood cells and gut epithelial ... ...

Abstract	We integrated ubiquity, mass and lifespan of all major cell types to achieve a comprehensive quantitative description of cellular turnover. We found a total cellular mass turnover of 80 ± 20 grams per day, dominated by blood cells and gut epithelial cells. In terms of cell numbers, close to 90% of the (0.33 ± 0.02) × 10
MeSH term(s)	Blood Cells/cytology ; Cellular Senescence ; Epithelial Cells/cytology ; Humans
Language	English
Publishing date	2021-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-020-01182-9
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Article ; Online: The unmitigated profile of COVID-19 infectiousness.

Sender, Ron / Bar-On, Yinon / Park, Sang Woo / Noor, Elad / Dushoff, Jonathan / Milo, Ron

eLife

2022 Volume 11

Abstract: Quantifying the temporal dynamics of infectiousness of individuals infected with SARS-CoV-2 is crucial for understanding the spread of COVID-19 and for evaluating the effectiveness of mitigation strategies. Many studies have estimated the infectiousness ... ...

Abstract	Quantifying the temporal dynamics of infectiousness of individuals infected with SARS-CoV-2 is crucial for understanding the spread of COVID-19 and for evaluating the effectiveness of mitigation strategies. Many studies have estimated the infectiousness profile using observed serial intervals. However, statistical and epidemiological biases could lead to underestimation of the duration of infectiousness. We correct for these biases by curating data from the initial outbreak of the pandemic in China (when mitigation was minimal), and find that the infectiousness profile of the original strain is longer than previously thought. Sensitivity analysis shows our results are robust to model structure, assumed growth rate and potential observational biases. Although unmitigated transmission data is lacking for variants of concern (VOCs), previous analyses suggest that the alpha and delta variants have faster within-host kinetics, which we extrapolate to crude estimates of variant-specific unmitigated generation intervals. Knowing the unmitigated infectiousness profile of infected individuals can inform estimates of the effectiveness of isolation and quarantine measures. The framework presented here can help design better quarantine policies in early stages of future epidemics.
MeSH term(s)	COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/transmission ; COVID-19/virology ; Humans ; Quarantine ; SARS-CoV-2/pathogenicity
Language	English
Publishing date	2022-08-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.79134
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Article ; Online: The unmitigated profile of COVID-19 infectiousness

Ron Sender / Yinon Bar-On / Sang Woo Park / Elad Noor / Jonathan Dushoff / Ron Milo

eLife, Vol

2022 Volume 11

Abstract	Quantifying the temporal dynamics of infectiousness of individuals infected with SARS-CoV-2 is crucial for understanding the spread of COVID-19 and for evaluating the effectiveness of mitigation strategies. Many studies have estimated the infectiousness profile using observed serial intervals. However, statistical and epidemiological biases could lead to underestimation of the duration of infectiousness. We correct for these biases by curating data from the initial outbreak of the pandemic in China (when mitigation was minimal), and find that the infectiousness profile of the original strain is longer than previously thought. Sensitivity analysis shows our results are robust to model structure, assumed growth rate and potential observational biases. Although unmitigated transmission data is lacking for variants of concern (VOCs), previous analyses suggest that the alpha and delta variants have faster within-host kinetics, which we extrapolate to crude estimates of variant-specific unmitigated generation intervals. Knowing the unmitigated infectiousness profile of infected individuals can inform estimates of the effectiveness of isolation and quarantine measures. The framework presented here can help design better quarantine policies in early stages of future epidemics.
Keywords	COVID-19 ; SARS-CoV-2 ; generation interval ; epidemiology ; mitigation ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The total mass, number, and distribution of immune cells in the human body.

Sender, Ron / Weiss, Yarden / Navon, Yoav / Milo, Idan / Azulay, Nofar / Keren, Leeat / Fuchs, Shai / Ben-Zvi, Danny / Noor, Elad / Milo, Ron

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 44, Page(s) e2308511120

Abstract: The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. Here, we estimated the abundance of the primary immune cell types ... ...

Abstract	The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. Here, we estimated the abundance of the primary immune cell types throughout all tissues in the human body. We conducted a literature survey and integrated data from multiplexed imaging and methylome-based deconvolution. We also considered cellular mass to determine the distribution of immune cells in terms of both number and total mass. Our results indicate that the immune system of a reference 73 kg man consists of 1.8 × 10
MeSH term(s)	Male ; Humans ; Human Body ; Lymphocytes ; Lymph Nodes ; Spleen ; Macrophages
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2308511120
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Article ; Online: The global biomass of wild mammals.

Greenspoon, Lior / Krieger, Eyal / Sender, Ron / Rosenberg, Yuval / Bar-On, Yinon M / Moran, Uri / Antman, Tomer / Meiri, Shai / Roll, Uri / Noor, Elad / Milo, Ron

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 10, Page(s) e2204892120

Abstract: Wild mammals are icons of conservation efforts, yet there is no rigorous estimate available for their overall global biomass. Biomass as a metric allows us to compare species with very different body sizes, and can serve as an indicator of wild mammal ... ...

Abstract	Wild mammals are icons of conservation efforts, yet there is no rigorous estimate available for their overall global biomass. Biomass as a metric allows us to compare species with very different body sizes, and can serve as an indicator of wild mammal presence, trends, and impacts, on a global scale. Here, we compiled estimates of the total abundance (i.e., the number of individuals) of several hundred mammal species from the available data, and used these to build a model that infers the total biomass of terrestrial mammal species for which the global abundance is unknown. We present a detailed assessment, arriving at a total wet biomass of ≈20 million tonnes (Mt) for all terrestrial wild mammals (95% CI 13-38 Mt), i.e., ≈3 kg per person on earth. The primary contributors to the biomass of wild land mammals are large herbivores such as the white-tailed deer, wild boar, and African elephant. We find that even-hoofed mammals (artiodactyls, such as deer and boars) represent about half of the combined mass of terrestrial wild mammals. In addition, we estimated the total biomass of wild marine mammals at ≈40 Mt (95% CI 20-80 Mt), with baleen whales comprising more than half of this mass. In order to put wild mammal biomass into perspective, we additionally estimate the biomass of the remaining members of the class Mammalia. The total mammal biomass is overwhelmingly dominated by livestock (≈630 Mt) and humans (≈390 Mt). This work is a provisional census of wild mammal biomass on Earth and can serve as a benchmark for human impacts.
MeSH term(s)	Humans ; Animals ; Swine ; Deer ; Biomass ; Cetacea ; Caniformia ; Sus scrofa
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2204892120
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Article: The total number and mass of SARS-CoV-2 virions.

Sender, Ron / Bar-On, Yinon M / Gleizer, Shmuel / Bernsthein, Biana / Flamholz, Avi / Phillips, Rob / Milo, Ron

medRxiv : the preprint server for health sciences

2021

Abstract: Quantitatively describing the time course of the SARS-CoV-2 infection within an infected individual is important for understanding the current global pandemic and possible ways to combat it. Here we integrate the best current knowledge about the typical ... ...

Abstract	Quantitatively describing the time course of the SARS-CoV-2 infection within an infected individual is important for understanding the current global pandemic and possible ways to combat it. Here we integrate the best current knowledge about the typical viral load of SARS-CoV-2 in bodily fluids and host tissues to estimate the total number and mass of SARS-CoV-2 virions in an infected person. We estimate that each infected person carries 10
Language	English
Publishing date	2021-04-05
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.11.16.20232009
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Article ; Online: The total number and mass of SARS-CoV-2 virions.

Sender, Ron / Bar-On, Yinon M / Gleizer, Shmuel / Bernshtein, Biana / Flamholz, Avi / Phillips, Rob / Milo, Ron

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 25

Abstract: Quantitatively describing the time course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within an infected individual is important for understanding the current global pandemic and possible ways to combat it. Here we ... ...

Abstract	Quantitatively describing the time course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within an infected individual is important for understanding the current global pandemic and possible ways to combat it. Here we integrate the best current knowledge about the typical viral load of SARS-CoV-2 in bodily fluids and host tissues to estimate the total number and mass of SARS-CoV-2 virions in an infected person. We estimate that each infected person carries 10
MeSH term(s)	COVID-19/virology ; Humans ; SARS-CoV-2/physiology ; Serologic Tests ; Viral Load ; Virion/physiology
Language	English
Publishing date	2021-06-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2024815118
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Article ; Online: Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans.

Sender, Ron / Fuchs, Shai / Milo, Ron

Cell

2016 Volume 164, Issue 3, Page(s) 337–340

Abstract: It is often presented as common knowledge that, in the human body, bacteria outnumber human cells by a ratio of at least 10:1. Revisiting the question, we find that the ratio is much closer to 1:1. ...

Abstract	It is often presented as common knowledge that, in the human body, bacteria outnumber human cells by a ratio of at least 10:1. Revisiting the question, we find that the ratio is much closer to 1:1.
MeSH term(s)	Adult ; Bacteria/cytology ; Bacterial Physiological Phenomena ; Body Weight ; Cell Count ; Colon/microbiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Microbiota ; Symbiosis
Language	English
Publishing date	2016-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2016.01.013
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Article ; Online: Revised Estimates for the Number of Human and Bacteria Cells in the Body.

Sender, Ron / Fuchs, Shai / Milo, Ron

PLoS biology

2016 Volume 14, Issue 8, Page(s) e1002533

Abstract: Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial ... ...

Abstract	Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg.
MeSH term(s)	Adult ; Bacteria/cytology ; Bacteria/growth & development ; Bacterial Load ; Body Weights and Measures ; Cell Count ; Humans ; Male ; Microbiota ; Organ Specificity
Language	English
Publishing date	2016-08-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.1002533
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