Systems Biology

The PP2A-like phosphatase Ppg1 mediates assembly of the Far complex to balance gluconeogenic outputs and adapt to glucose depletion

1. Shreyas Niphadkar
2. Lavanya Karinje
3. Sunil Laxman

Reviewed by Review Commons

Quantitative Geometric Modeling of Blood Cells from X-ray Histotomograms of Whole Zebrafish Larvae

1. Maksim A. Yakovlev
2. Ke Liang
3. Carolyn R. Zaino
4. Daniel J. Vanselow
5. Andrew L. Sugarman
6. Alex Y. Lin
7. Patrick J. La Riviere
8. Yuxi Zheng
9. Justin D. Silverman
10. John C. Leichty
11. Sharon X. Huang
12. Keith C. Cheng

• Curated by eLife

  eLife assessment

  Tissue phenotyping is central to nearly all areas of biology. In this study, the authors use an advanced form of micro-CT (X-ray histotomography) in zebrafish to phenotype blood cells in the intact animal. These approaches build upon prior work from this group and others showing this is a scalable imaging method that could readily be applied to other cell types, and provide an excellent complement to histological analysis of tissues. This is important work, as it demonstrates that the method can provide an approach that is orthogonal to conventional histology. The strength of the presented data is compelling, with description of both the hardware and software needed to implement the protocol, which will make it accessible to other researchers in the field.

Reviewed by eLife

Affected cell types for hundreds of Mendelian diseases revealed by analysis of human and mouse single-cell data

1. Idan Hekselman
2. Assaf Vital
3. Maya Ziv-Agam
4. Lior Kerber
5. Ido Yairi
6. Esti Yeger-Lotem

• Curated by eLife

  eLife assessment

  The study presents analyses linking cell-types to monogenic disorders using over-expression of known disease-associated genes in single-cell data to identify 110 disease-affected cell types for 714 Mendelian diseases. Overall this important study combines multiple data analyses to quantify the connection between cell types and human disorders. While some of the analyses are compelling, updates to the method are needed to ensure that statistical inference is appropriately stringent and rigorous.

Reviewed by eLife

Multicellular factor analysis of single-cell data for a tissue-centric understanding of disease

1. Ricardo Omar Ramirez Flores
2. Jan David Lanzer
3. Daniel Dimitrov
4. Britta Velten
5. Julio Saez-Rodriguez

Reviewed by Review Commons

Homeostasis, injury, and recovery dynamics at multiple scales in a self-organizing mouse intestinal crypt

1. Louis Gall
2. Carrie Duckworth
3. Ferran Jardi
4. Lieve Lammens
5. Aimee Parker
6. Ambra Bianco
7. Holly Kimko
8. David Mark Pritchard
9. Carmen Pin

• Curated by eLife

  eLife assessment

  The authors developed a valuable mathematical model that describes the spatiotemporal dynamics of cells in the intestinal crypt. The proposed model makes an important contribution to the field, allowing a better understanding of the formation and response dynamics of the intestinal crypt through the effective evaluation of health, disease, and treatment conditions. The authors provided solid evidence of the validity of their model and their conclusions, but some minor claims are not properly justified in the current manuscript. This paper is meant for computational biologists and cancer researchers working on oncotherapies for the intestinal epithelium.

Reviewed by eLife

Systems level identification of a matrisome-associated macrophage polarisation state in multi-organ fibrosis

1. John F Ouyang
2. Kunal Mishra
3. Yi Xie
4. Harry Park
5. Kevin Y Huang
6. Enrico Petretto
7. Jacques Behmoaras

• Curated by eLife

  eLife assessment

  This important study deepens our understanding of macrophage phenotypes in pathological contexts and identifies a new macrophage state associated with tissue fibrosis, as well as putative drivers of this cellular state. The authors provide convincing evidence and performed a well-thought-out and thoroughly described computational analysis of single-cell RNA-sequencing data. This work will be of broad interest to the fields of tissue inflammation, fibrosis, macrophage biology, and immunology.

Reviewed by eLife

A Phosphoproteomics Data Resource for Systems-level Modeling of Kinase Signaling Networks

1. Song Feng
2. James A. Sanford
3. Thomas Weber
4. Chelsea M. Hutchinson-Bunch
5. Panshak P. Dakup
6. Vanessa L. Paurus
7. Kwame Attah
8. Herbert M. Sauro
9. Wei-Jun Qian
10. H. Steven Wiley

Reviewed by preLights

A new pipeline SPICE identifies novel JUN-IKZF1 composite elements

1. Peng Li
2. Sree H. Pulugulla
3. Sonali Das
4. Jangsuk Oh
5. Rosanne Spolski
6. Jian-Xin Lin
7. Warren J. Leonard

• Curated by eLife

  eLife assessment

  This valuable study presents a screening pipeline (SPICE) for detecting DNA motif spacing preferences between TF partners. SPICE predicts previously known composite elements, but experiments to elucidate the nature of the predicted novel interaction between JUN and IKZF1 are incomplete. These experiments would benefit from more rigorous approaches using other databases to explore additional relevant data. The work will be of broad interest to those involved in dissecting the regulatory logic of mammalian enhancers and promoters.

Reviewed by eLife

Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting

1. Thiruma V Arumugam
2. Asfa Alli-Shaik
3. Elisa A Liehn
4. Sharmelee Selvaraji
5. Luting Poh
6. Vismitha Rajeev
7. Yoonsuk Cho
8. Yongeun Cho
9. Jongho Kim
10. Joonki Kim
11. Hannah LF Swa
12. David Tan Zhi Hao
13. Chutima Rattanasopa
14. David Yang-Wei Fann
15. David Castano Mayan
16. Gavin Yong-Quan Ng
17. Sang-Ha Baik
18. Karthik Mallilankaraman
19. Mathias Gelderblom
20. Grant R Drummond
21. Christopher G Sobey
22. Brian K Kennedy
23. Roshni R Singaraja
24. Mark P Mattson
25. Dong-Gyu Jo
26. Jayantha Gunaratne

• Curated by eLife

  eLife assessment

  This study provides a useful catalog of the cardiac proteome and transcriptome in response to intermittent fasting. Although mechanistic integration is limited, the technical aspects have been executed in a solid way, and sufficient evidence is provided to support the main conclusions. Future work can build on this study to expand our understanding of the relationship between dietary perturbations and cardiac function.

Reviewed by eLife

A statistical framework for quantifying the nuclear export rate of influenza viral mRNAs

1. Michi Miura
2. Naho Kiuchi
3. Siu-Ying Lau
4. Bobo Wing-Yee Mok
5. Hiroshi Ushirogawa
6. Tadasuke Naito
7. Honglin Chen
8. Mineki Saito

• Curated by eLife

  eLife assessment

  This important study combines virology experiments and mathematical modeling to determine the nuclear export rate of each of the eight RNA segments of the influenza A virus, leading to the proposal that a specific retention of mRNA within the nucleus delays the expression of antigenic viral proteins. The proposed model for explaining the differential rate of export is compelling, going beyond the state of the art, but the experimental setup is incomplete and would benefit from additional approaches. The insight so far is interesting, but because in the end it is left as an observation, the overall advance remains limited.

Reviewed by eLife