Scientific papers as open discovery tools

EMBO Scientific Publishing

Thomas Lemberger

Chief Editor, Molecular Systems Biology

Deputy Head of Publications, EMBO

1. Editorial Process

2. Scientific integrity

3. Integrating data in papers

Scientific publishing

“The publication of scientific information is intended to move science forward. More specifically, the act of publishing is a quid pro quo in which authors receive credit and acknowledgment in exchange for disclosure of their scientific findings.”

disclose findings

credit

move science forward

critical evaluation

editorial process

editorial process @EMBO

EMBO Scientific Publications

• All areas of molecular & cell biology

• First journal launched by EMBO (1982)

•All areas of molecular & cell biology

•Short-format papers

•Science & Society section

•At the interface between basic and clinical life sciences

•Open Access

•Systems biology, synthetic biology, systems medicine

•Open Access

quality

quality

community

EMBO Editors:Thomas LembergerMaria Polychronidou

R Aebersold

GM Church

L Hood

E Liu

P Bork

Julie AhringerCharles AuffrayEwan BirneyTom BlundellThomas S. DeisboeckJan EllenbergMichael ElowitzAlan FershtStan FieldsMark GersteinFrank HolstegeSung Hou KimHiroaki KitanoDoron LancetAndrew J. LinkStephen OliverJeremy NicholsonBernhard PalssonRama RanganathanUwe SauerLuis SerranoLucy ShapiroPamela SilverMichael SnyderJanet ThorntonMasaru TomitaMarc VidalHans V. WesterhoffLothar WillmitzerJohn Yates

Senior Editors Advisory Board

Scope & general policies

OPENACCESS

The editorial process

editorialrejection

review

reject revise

reject accept

time

First editorial decision

editorialrejection

review

reject revise

reject accept

time

First editorial decision

EMBO editors read the entire manuscript (yes!)

Decision on a balance of multiple factors:

• Scope• Novelty & conceptual advance• Mechanistic, functional, biological insights• Utility of methods, dataset, resource• Completeness and conclusiveness of the analysis

In case of doubt...R Aebersold

GM Church

L Hood

E Liu

P Bork

Julie AhringerCharles AuffrayEwan BirneyTom BlundellThomas S. DeisboeckJan EllenbergMichael ElowitzAlan FershtStan FieldsMark GersteinFrank HolstegeSung Hou KimHiroaki KitanoDoron LancetAndrew J. LinkStephen OliverJeremy NicholsonBernhard PalssonRama RanganathanUwe SauerLuis SerranoLucy ShapiroPamela SilverMichael SnyderJanet ThorntonMasaru TomitaMarc VidalHans V. WesterhoffLothar WillmitzerJohn Yates

Senior Editors Advisory Board

EMBO Editors:Thomas LembergerMaria Polychronidou

Initial editorial decision

To review or not to review...

editorialrejection

review

reject revise

reject accept

time

Peer-review

Referees are invited based on:

• Balance of expertise• Reputation as researcher• Reputation as reviewer• No conflict of interest (positive or negative)

3 (4) reviewers / manuscript

Transparent peer review

1. Summary• Describe your understanding of the story• What are the key conclusions: findings and concepts• What are the methodology and model system

2. General remarks• Are you convinced of the key conclusions?• Place the work in its context.• What is the nature of the advance (conceptual, technical, clinical)?• How important is the advance as compared to previous knowledge?• What audience will be interested in this?

3. Major points• Specific criticisms related to key conclusions• Specify experiments or analyses required to demonstrate the conclusions• Motivate your critique with relevant citations and argumentation

4. Minor points• Easily addressable points• Presentation and style• Trivial mistakes

Referee report

Referee report: example

Editorial decision letter:

Cross-commenting

reviewersreviewersreportsreports

authors

“…[it] settles a controversy in the field which has been going on for more than ten years. In summary, this is a landmark paper. I cannot support publication in your journal strongly enough!”

“As written, the paper is focused on the methods, which is fine given that's where it makes its most substantial contribution. But the writing is quite technical and could benefit from more explanation of the high-level logic of their approach.”

“After reading through this nicely-executed technical work, one is left with an impression that after all we really have not gained much new mechanistic insights.…in addition to the XXX data that should be generated under their current framework…”

…Each reviewer has numerous suggestions about how to do this. It will likely be impossible to incorporate them all while retaining a coherent narrative. […]

Reviewer 3 also calls for an additional experiment - including XXX stains in the current dataset. To incorporate this into their current analytical framework, the authors would have to find parameters and reagents to allow simultaneous imaging of 5 genes (not just the 4 presented here). Moreover, they would then have to reacquire all images using the 5-stain protocol.

While I agree that it would be useful to have XXX data included, I also believe that this is beyond the scope of this paper.

Ref

#1

Ref

#2

Ref

#3

Ref #2 cross-comments

Cross-commenting

Post-revision review

editorialrejection

review

reject revise

reject accept

time

Transparent Process• Transparent Anonymous Peer Review:

Anonymous referee reports and editorial correspondence are published alongside papers

• Single Round of Major Revision:More than 90% of invited revisions are published at Molecular Systems Biology

• Referee Discussion before Decision:Referees are invited to comment on each other's reports before the editor makes a decision

• Scooping Protection:Findings that are published by others during review or revision are not a criterion for rejection

• Source Data for Figures:Authors can archive and make available the data underlying their published figures

• Flexible Formatting:No journal-specific formatting required at submission


“The publication of scientific information is intended to move science forward. More specifically, the act of publishing is a quid pro quo in which authors receive credit and acknowledgment in exchange for disclosure of their scientific findings.”


The publication of scientific information is intended to move science forward. More specifically, the act of publishing is a quid pro quo in which authors receive credit and acknowledgment in exchange for disclosure of their scientific findings.

Implies:•Originality•Integrity•Authenticity

Respect of:•Laws and ethics•Safety and security•Societal context

Beautification Fabrication

• Clarification • Aesthetics

• Deliberate manufacturin of data

Data integrity

Selective reporting

• Misrepresentation of the data

• Biasing data to fit a particular hypothesis

New submission:

Seoul National University's report on Dr. Hwang Woo Suk:

The data in the 2005 article including test results from •DNA fingerprinting, •photographs of teratoma,•embryoid bodies, •MHC-HLA isotype matches and•karyotyping have all been fabricated.

http://www.useoul.edu/snunews?bm=v&bbsidx=71494&page=63

Figure 2F Figure 6D

(D) Human NT-ESCs expressed standard pluripotency markers detected by immunocytochemistry for antibodies against OCT4, NANOG, SOX2, SSEA-4, TRA-1–60, and TRA-1–81. Original magnification, ×200; Ph, phase contrast.

(F) NT-ESC colony with typical morphology derived from a caffeine-treated SCNT human blastocyst.

Figure 2F Figure 6D

(D) Human NT-ESCs expressed standard pluripotency markers detected by immunocytochemistry for antibodies against OCT4, NANOG, SOX2, SSEA-4, TRA-1–60, and TRA-1–81. Original magnification, ×200; Ph, phase contrast. Note that the upper-left image for hESO-NT1 is the same shown in Figure 2F.

(F) NT-ESC colony with typical morphology derived from a caffeine-treated SCNT human blastocyst.

In Figures 2F and S5 (upper-right), we presented two phase-contrast photos of fields of cells, correctly labeled as SCNT-derived hESO-NT1 and IVF-derived hESO-7, respectively. These images are the same fields of cells shown in the top two images of Figure 6D; however, in Figure 6D, we inadvertently switched the labels on the images. This re-use of the images was intentional, but we should have indicated this in the original legend for Figure 6. We have corrected the labeling error in Figure 6D.

We would also like to note that the Scientific Integrity Committee at Oregon Health & Science University has carefully assessed the paper and the errors and has concluded that there is no evidence of fabrication, falsification, or plagiarism that would warrant further inquiry or investigation into research misconduct.

In Figures 2F and S5 (upper-right), we presented two phase-contrast photos of fields of cells, correctly labeled as SCNT-derived hESO-NT1 and IVF-derived hESO-7, respectively. These images are the same fields of cells shown in the top two images of Figure 6D; however, in Figure 6D, we inadvertently switched the labels on the images. This re-use of the images was intentional, but we should have indicated this in the original legend for Figure 6. We have corrected the labeling error in Figure 6D.

We would also like to note that the Scientific Integrity Committee at Oregon Health & Science University has carefully assessed the paper and the errors and has concluded that there is no evidence of fabrication, falsification, or plagiarism that would warrant further inquiry or investigation into research misconduct.

• Provide guidance to students and postdocs• View original data • Organize good data management practice• Maintain an open lab environment• Accept only relevant authorship• Cooperate with editors• Retract/correct as appropriate

What can PIs do?

• Rigorous peer review• Check by editors before publication• Investigation and retraction policy• Data transparency

What can journals do?

Title

Abstract

Synopsis

Main paper

‘Expanded view’

Datasets & code

What is a paper?

A scientific result converted into a collection of pixels…

8/27

What is a figure?

•Data archival

service

•Data‘transparency’

•Data reuse

•Data-oriented

search

(Level 0:metadata associated to individual panels.)

Level 1: ‘object-oriented’ representation of experimental variables as a list of chemical and biological components.

Level 2: represent the causality of the experimental design: “Measurement of Y as a function of A, B, C, using assay P in biological system S.”

Level 3: machine-readable representation with standard identifiers.

measured componentmeasured component

perturbed componentperturbed component

experimental system

15/27

assayed property

Structured metadata:‘perturbation-observation-assay’

Tools to publish figures as structured digital objects

that link the human-readable illustrations with

machine-readable metadata and ‘source data’ in

order to

•improve data transparency;

•make published data useable;

•enable data-oriented search.

9/27

SourceData

Resulting hypothesis: test drug Z in disease D.

tissue Ttissue T disease D

disease D

gene xgene x

Pap

er 3

protein X protein X PPkinase Ykinase Y

Pap

er 2

kinase Ykinase Y activityactivitydrug Zdrug Z

Pap

er 1

Data-oriented search

19/27

Smad3

Hey1

TGFbetaVE-cdh

Rad51 foci

AR

Tsc2

1 4

6 2 5

3

1,4

4

5

6

2

…

…

Rad51Nuclear

complexesTGFb, Smad3


• Dominant channel for the dissemination of peer-reviewed data.

• Journals function as a proxy for quality in research assessment

• The rate of publishing keeps

increasing.• Papers are human-readable but

poorly machine-readable.

search

The Paper of the Future?

<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" "archivearticle.dtd"><article article-type="research-article"><?properties no_embargo?> <front> <journal-meta> <journal-id journal-id-type="nlm-ta">Mol Syst Biol</journal-id> <journal-title>Molecular Systems Biology</journal-title> <issn pub-type="epub">1744-4292</issn> <publisher> <publisher-name>Nature Publishing Group</publisher-name> </publisher> </journal-meta> <article-meta> <article-id pub-id-type="pmc">2238715</article-id>

Search

Future directions in systems biology

• Genome-wide genetics of human diseases • Translational systems biology or systems

medicine• Genome-scale engineering & synthetic biology• Temporal structure of biological processes• ‘In vivo biochemistry’ with single-cell single-

molecule assays• Bridge the gap between ‘omics’ and mechanistic

models

“How do we get from the Jimome & Craigome to systems biology?”George M Church, Senior Editor

Multi-omics data integrationIntegration of clinical data with a genome-scale metabolic model of the human adipocyte.Jens Nielsen and colleagues, Mol Syst Biol. 2013;9:649.

Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells.Zuzana Storchova, Mol Syst Biol. 2012 8:608.

Comparative omics for functional discoveries

19 0

17 h

uman

gen

es

Phylogenetic profiles of across 86 eukaryotic genomes.

Human disease locus discovery and mapping to molecular pathways through phylogenetic profiling.

Gary Ruvkun and colleagues, Mol Syst Biol. 2013 9:692

??

Beyond the hairball

Costanzo et al, Science 2010 Hoog et al, Dev Cell 2007

Spatial patterns

Di Vetura and Sourjik , 2011 Mol Syst Biol 7:457

Waks et al, 2011 Mol Syst Biol 7:506

Temporal patternsPromoter decoding of transcription factor dynamics involves a trade-off between noise and control of gene expression.Hansen AS, O'Shea EK. Mol Syst Biol. 2013 9:704

Cell population & dynamicsDigital cell quantification identifies global immune cell dynamics during influenza infection.Ido Amit and colleagues, 2014 Mol Syst Biol. 10:720

Microbiome & metagenomicsA top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model.J. Nicholson and colleagues, Mol Syst Biol. 2007 3:112.

Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data.Peer Bork and colleagues, Mol Syst Biol. 2011 7:473

Synthetic biologySynthesizing a novel genetic sequential logic circuit: a push-on push-off switch.Qi Ouyang (Beijing University), Mol Syst Biol. 2010;6:350.

Genome-scale engineeringGenome-scale engineering for systems and synthetic biology.Esvelt KM, Wang HH, Mol Syst Biol. 2013 9:641.

Scientific papers as open discovery tools

Technology

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