The Case For and Against Double-blind Reviews, bioRxiv, 2018-12-16
To date, the majority of authors on scientific publications have been men. While much of this gender bias can be explained by historic sexism and discrimination, there is concern that women may still be disadvantaged by the peer review process if reviewers' unconscious biases lead them to reject publications with female authors more often. One potential solution to this perceived gender bias in the reviewing process is for journals to adopt double-blind reviews whereby neither the authors nor the reviewers are aware of each other's identities and genders. To test the efficacy of double-blind reviews, we assigned gender to every authorship of every paper published in 5 different journals with different peer review processes (double-blind vs. single blind) and subject matter (birds vs. behavioral ecology) from 2010-2018 (n = 4865 papers). While female authorships comprised only 35% of the total, the double-blind journal Behavioral Ecology did not have more female authorships than its single-blind counterparts. Interestingly, the incidence of female authorship is higher at behavioral ecology journals (Behavioral Ecology and Behavioral Ecology and Sociobiology) than in the ornithology journals (Auk, Condor, Ibis), for papers on all topics as well as those on birds. These analyses suggest that double-blind review does not currently increase the incidence of female authorship in the journals studied here. We conclude, at least for these journals, that double-blind review does not benefit female authors and may, in the long run, be detrimental.
biorxiv scientific-communication-and-education 100-200-users 2018Large-scale analyses of human microbiomes reveal thousands of small, novel genes and their predicted functions, bioRxiv, 2018-12-14
AbstractSmall proteins likely abound in prokaryotes, and may mediate much of the communication that occurs between organisms within a microbiome and their host. Unfortunately, small proteins are traditionally overlooked in biology, in part due to the computational and experimental difficulties in detecting them. To systematically identify novel small proteins, we carried out a large comparative genomics study on 1,773 HMP human-associated metagenomes from four different body sites (mouth, gut, skin and vagina). We describe more than four thousand conserved protein families, the majority of which are novel; ~30% of these protein families are predicted to be secreted or transmembrane. Over 90% of the small protein families have no known domain, and almost half are not represented in reference genomes, emphasizing the incompleteness of knowledge in this space. Our analysis exposes putative novel ‘housekeeping’ small protein families, including a potential novel ribosomally associated protein, as well as ‘mammalian-specific’ or ‘human-specific’ protein families. By analyzing the genomic neighborhood of small genes, we pinpoint a subset of families that are potentially associated with defense against bacteriophage. Finally, we identify families that may be subject to horizontal transfer and are thus potentially involved in adaptation of bacteria to the changing human environment. Our study suggest that small proteins are highly abundant and that those of the human microbiome, in particular, may perform diverse functions that have not been previously reported.
biorxiv microbiology 0-100-users 2018Population structure of modern-day Italians reveals patterns of ancient and archaic ancestries in Southern Europe, bioRxiv, 2018-12-14
European populations display low genetic diversity as the result of long term blending of the small number of ancient founding ancestries. However it is still unclear how the combination of ancient ancestries related to early European foragers, Neolithic farmers and Bronze Age nomadic pastoralists can fully explain genetic variation across Europe. Populations in natural crossroads like the Italian peninsula are expected to recapitulate the overall continental diversity, but to date have been systematically understudied. Here we characterised the ancestry profiles of modern-day Italian populations using a genome-wide dataset representative of modern and ancient samples from across Italy, Europe and the rest of the world. Italian genomes captured several ancient signatures, including a non-steppe related substantial ancestry contribution ultimately from the Caucasus. Differences in ancestry composition as the result of migration and admixture generated in Italy the largest degree of population structure detected so far in the continent and shaped the amount of Neanderthal DNA present in modern-day populations.
biorxiv genomics 0-100-users 2018An RNA-binding region regulates CTCF clustering and chromatin looping, bioRxiv, 2018-12-13
Mammalian genomes are folded into Topologically Associating Domains (TADs), consisting of cell-type specific chromatin loops anchored by CTCF and cohesin. Since CTCF and cohesin are expressed ubiquitously, how cell-type specific CTCF-mediated loops are formed poses a paradox. Here we show RNase-sensitive CTCF self-association in vitro and that an RNA-binding region (RBR) mediates CTCF clustering in vivo. Intriguingly, deleting the RBR abolishes or impairs almost half of all chromatin loops in mouse embryonic stem cells. Disrupted loop formation correlates with abrogated clustering and diminished chromatin binding of the RBR mutant CTCF protein, which in turn results in a failure to halt cohesin-mediated extrusion. Thus, CTCF loops fall into at least 2 classes RBR-independent and RBR-dependent loops. We suggest that evidence for distinct classes of RBR-dependent loops may provide a mechanism for establishing cell-specific CTCF loops regulated by RNAs and other RBR partner.
biorxiv biophysics 200-500-users 2018Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy, bioRxiv, 2018-12-13
SummaryThe success of immunotherapy has led to a myriad of new clinical trials. Connected to these trials are efforts to discover biomarkers providing mechanistic insight and predictive signatures for personalization. Still, the plethora of immune monitoring technologies can face investigator bias, missing unanticipated cellular responses in limited clinical material. We here present a mass cytometry workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate human immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. The resulting assay enumerated ≥ 98% of peripheral immune cells with ≥ 4 positively identifying antigens. Robustness and reproducibility were demonstrated on multiple samples types, across research centers and by orthogonal measurements. Using automated analysis, we monitored complex immune dynamics, identifying signatures in bone-marrow transplantation associated graft-versus-host disease. This validated and available workflow ensures comprehensive immunophenotypic analysis, data comparability and will accelerate biomarker discovery in immunomodulatory therapeutics.
biorxiv immunology 100-200-users 2018