PLoS Collections: New Articles

In the Tradition of Science: An Interview with Victor Ambros

2010-03-05T08:00:00Z

Ten Simple Rules for Organizing a Virtual Conference—Anywhere

2010-02-26T08:00:00Z

How to Understand the Cell by Breaking It: Network Analysis of Gene Perturbation Screens

2010-02-26T08:00:00Z

A New Horned Crocodile from the Plio-Pleistocene Hominid Sites at Olduvai Gorge, Tanzania

2010-02-24T08:00:00Z

Background

The fossil record reveals surprising crocodile diversity in the Neogene of Africa, but relationships with their living relatives and the biogeographic origins of the modern African crocodylian fauna are poorly understood. A Plio-Pleistocene crocodile from Olduvai Gorge, Tanzania, represents a new extinct species and shows that high crocodylian diversity in Africa persisted after the Miocene. It had prominent triangular “horns” over the ears and a relatively deep snout, these resemble those of the recently extinct Malagasy crocodile Voay robustus, but the new species lacks features found among osteolaemines and shares derived similarities with living species of Crocodylus.

Methodology/Principal Findings

The holotype consists of a partial skull and skeleton and was collected on the surface between two tuffs dated to approximately 1.84 million years (Ma), in the same interval near the type localities for the hominids Homo habilis and Australopithecus boisei. It was compared with previously-collected material from Olduvai Gorge referable to the same species. Phylogenetic analysis places the new form within or adjacent to crown Crocodylus.

Conclusions/Significance

The new crocodile species was the largest predator encountered by our ancestors at Olduvai Gorge, as indicated by hominid specimens preserving crocodile bite marks from these sites. The new species also reinforces the emerging view of high crocodylian diversity throughout the Neogene, and it represents one of the few extinct species referable to crown genus Crocodylus.

PLoS ONE: The DREAM3 systems biology challenges: a Dialogue for Reverse Engineering Assessment and Methods

2010-02-23T08:00:00Z

This Collection contains those papers representing the output of the best performing methods of the DREAM3 challenges, which themselves were discussed and presented at the third DREAM (Dialogue for Reverse Engineering Assessment and Methods) conference, held in late 2008 in Cambridge, MA.

Systems biology has embraced computational modeling in response to the quantitative nature and increasing scale of contemporary data sets; however, the volume of data being generated is accelerating as molecular profiling technology evolves. Computational algorithms play a prominent role in the interpretation of systems biology data and so the Dialogue for Reverse Engineering Assessments and Methods (DREAM) is a community effort to catalyze discussion about the design, application, and assessment of systems biology models through annual conferences and reverse-engineering challenges. The various challenges, based on anonymized data sets, tested participants in network inference and prediction of measurements. The articles in this Collection describe the methods and strategies that achieved best performance in the DREAM3 challenges. The Collection as a whole summarizes the lessons learned by the community in the DREAM3 challenges and provides a much-needed context for interpreting claims of efficacy of algorithms described in the scientific literature.

DREAM is sponsored by Columbia University Center for Multiscale Analysis Genomic and Cellular Networks (MAGNet) and the IBM Computational Biology Center.

Image Credit: Gustavo Stolovitzky

Towards a Rigorous Assessment of Systems Biology Models: The DREAM3 Challenges

2010-02-23T08:00:00Z

Background

Systems biology has embraced computational modeling in response to the quantitative nature and increasing scale of contemporary data sets. The onslaught of data is accelerating as molecular profiling technology evolves. The Dialogue for Reverse Engineering Assessments and Methods (DREAM) is a community effort to catalyze discussion about the design, application, and assessment of systems biology models through annual reverse-engineering challenges.

Methodology and Principal Findings

We describe our assessments of the four challenges associated with the third DREAM conference which came to be known as the DREAM3 challenges: signaling cascade identification, signaling response prediction, gene expression prediction, and the DREAM3 in silico network challenge. The challenges, based on anonymized data sets, tested participants in network inference and prediction of measurements. Forty teams submitted 413 predicted networks and measurement test sets. Overall, a handful of best-performer teams were identified, while a majority of teams made predictions that were equivalent to random. Counterintuitively, combining the predictions of multiple teams (including the weaker teams) can in some cases improve predictive power beyond that of any single method.

Conclusions

DREAM provides valuable feedback to practitioners of systems biology modeling. Lessons learned from the predictions of the community provide much-needed context for interpreting claims of efficacy of algorithms described in the scientific literature.

Revised Lithostratigraphy of the Sonsela Member (Chinle Formation, Upper Triassic) in the Southern Part of Petrified Forest National Park, Arizona

2010-02-19T08:00:00Z

Background

Recent revisions to the Sonsela Member of the Chinle Formation in Petrified Forest National Park have presented a three-part lithostratigraphic model based on unconventional correlations of sandstone beds. As a vertebrate faunal transition is recorded within this stratigraphic interval, these correlations, and the purported existence of a depositional hiatus (the Tr-4 unconformity) at about the same level, must be carefully re-examined.

Methodology/Principal Findings

Our investigations demonstrate the neglected necessity of walking out contacts and mapping when constructing lithostratigraphic models, and providing UTM coordinates and labeled photographs for all measured sections. We correct correlation errors within the Sonsela Member, demonstrate that there are multiple Flattops One sandstones, all of which are higher than the traditional Sonsela sandstone bed, that the Sonsela sandstone bed and Rainbow Forest Bed are equivalent, that the Rainbow Forest Bed is higher than the sandstones at the base of Blue Mesa and Agate Mesa, that strata formerly assigned to the Jim Camp Wash beds occur at two stratigraphic levels, and that there are multiple persistent silcrete horizons within the Sonsela Member.

Conclusions/Significance

We present a revised five-part model for the Sonsela Member. The units from lowest to highest are: the Camp Butte beds, Lot's Wife beds, Jasper Forest bed (the Sonsela sandstone)/Rainbow Forest Bed, Jim Camp Wash beds, and Martha's Butte beds (including the Flattops One sandstones). Although there are numerous degradational/aggradational cycles within the Chinle Formation, a single unconformable horizon within or at the base of the Sonsela Member that can be traced across the entire western United States (the “Tr-4 unconformity”) probably does not exist. The shift from relatively humid and poorly-drained to arid and well-drained climatic conditions began during deposition of the Sonsela Member (low in the Jim Camp Wash beds), well after the Carnian-Norian transition.

Gene Expression Prediction by Soft Integration and the Elastic Net—Best Performance of the DREAM3 Gene Expression Challenge

2010-02-16T08:00:00Z

Background

To predict gene expressions is an important endeavour within computational systems biology. It can both be a way to explore how drugs affect the system, as well as providing a framework for finding which genes are interrelated in a certain process. A practical problem, however, is how to assess and discriminate among the various algorithms which have been developed for this purpose. Therefore, the DREAM project invited the year 2008 to a challenge for predicting gene expression values, and here we present the algorithm with best performance.

Methodology/Principal Findings

We develop an algorithm by exploring various regression schemes with different model selection procedures. It turns out that the most effective scheme is based on least squares, with a penalty term of a recently developed form called the “elastic net”. Key components in the algorithm are the integration of expression data from other experimental conditions than those presented for the challenge and the utilization of transcription factor binding data for guiding the inference process towards known interactions. Of importance is also a cross-validation procedure where each form of external data is used only to the extent it increases the expected performance.

Conclusions/Significance

Our algorithm proves both the possibility to extract information from large-scale expression data concerning prediction of gene levels, as well as the benefits of integrating different data sources for improving the inference. We believe the former is an important message to those still hesitating on the possibilities for computational approaches, while the latter is part of an important way forward for the future development of the field of computational systems biology.

The Extent of the Preserved Feathers on the Four-Winged Dinosaur Microraptor gui under Ultraviolet Light

2010-02-15T08:00:00Z

Background

The holotype of the theropod non-avian dinosaur Microraptor gui from the Early Cretaceous of China shows extensive preservation of feathers in a halo around the body and with flight feathers associated with both the fore and hindlimbs. It has been questioned as to whether or not the feathers did extend into the halo to reach the body, or had disassociated and moved before preservation. This taxon has important implications for the origin of flight in birds and the possibility of a four-winged gliding phase.

Methodology/Principal Findings

Examination of the specimen under ultraviolet light reveals that these feathers actually reach the body of the animal and were not disassociated from the bones. Instead they may have been chemically altered by the body tissues of the animal meaning that they did not carbonise close into the animal or more likely were covered by other decaying tissue, though evidence of their presence remains.

Conclusions/Significance

These UV images show that the feathers preserved on the slab are genuinely associated with the skeleton and that their arrangement and orientation is likely correct. The methods used here to reveal hidden features of the specimen may be applicable to other specimens from the fossil beds of Liaoning that produced Microraptor.

Characterizing Dynamic Changes in the Human Blood Transcriptional Network

2010-02-12T08:00:00Z

Author Summary

Peripheral blood is the most readily accessible human tissue for clinical studies and experimental research more generally. Large-scale molecular profiling technologies have enabled measurements of mRNA expression on the scale of whole genomes. Understanding the relationships between human blood gene expression profiles and clinical traits is extremely useful for inferring causal factors for human disease and for studying drug response. Biological pathways and the complex behaviors they induce are not static, but change dynamically in response to external factors such as intake/uptake of nutrients and administration of drugs. We employed a randomized, two-arm cross-over design to assess the effects of fasting and feeding on the dynamic changes of blood transcriptional network. Our work has convincingly shown that feeding or increasing nutritional load affects the human circadian rhythm system which connects to other biological processes including metabolic and immune responses. We believe this is a first step towards a more comprehensive population-based study that seeks to connect changes in the blood transcriptome to drug response, and to disease and biology more generally.