Validating module network learning algorithms using simulated data

In recent years, several authors have used probabilistic graphical models to learn expression modules and their regulatory programs from gene expression data. Here, we demonstrate the use of the synthetic data generator SynTReN for the purpose of testing and comparing module network learning algorithms. We introduce a software package for learning module networks, called LeMoNe, which incorporates a novel strategy for learning regulatory programs. Novelties include the use of a bottom-up Bayesian hierarchical clustering to construct the regulatory programs, and the use of a conditional entropy measure to assign regulators to the regulation program nodes. Using SynTReN data, we test the performance of LeMoNe in a completely controlled situation and assess the effect of the methodological changes we made with respect to an existing software package, namely Genomica. Additionally, we assess the effect of various parameters, such as the size of the data set and the amount of noise, on the inference performance. Overall, application of Genomica and LeMoNe to simulated data sets gave comparable results. However, LeMoNe offers some advantages, one of them being that the learning process is considerably faster for larger data sets. Additionally, we show that the location of the regulators in the LeMoNe regulation programs and their conditional entropy may be used to prioritize regulators for functional validation, and that the combination of the bottom-up clustering strategy with the conditional entropy-based assignment of regulators improves the handling of missing or hidden regulators.Comment: 13 pages, 6 figures + 2 pages, 2 figures supplementary informatio

Oligo-Miocene oxygen isotope and carbon record from IODP Site 342-U1406

These data contain a new high-resolution benthic foraminiferal oxygen isotope (d18Ob) record spanning ~26-22 Ma from Integrated Ocean Drilling Program Expedition 342 Site U1406 (Newfoundland Margin, Northwest Atlantic Ocean, ~40°N, 51°W; 3.8 km water depth). Oxygen isotopes of Cibicidoides mundulus (size range 125-250 micrometer) were generated using a Thermo Fisher Scientific MAT 253 mass-spectrometer coupled to a Thermo-Finnigan Kiel IV Carbonate Device in Southampton, Heidelberg, and Leipzig, and coupled to a Gasbench II in Frankfurt. International standards (NBS-18 and NBS-19) and in-house quality control standards were used to calibrate d18Ob. The record was astronomically tuned by recognising obliquity cycles in the X-ray fluorescence based CaCO3 record using newly generated coulometric carbonate content data (wt.% CaCO3), generated at the University of Southampton's Waterfront Campus, National Oceanography Centre Southampton (UoS-NOCS), using a CM5015 coulometer equipped with an AutoMate automated analysis devic

Large obliquity-paced Antarctic ice-volume fluctuations suggest melting by atmospheric and ocean warming during late Oligocene

Abstract The late Oligocene (~27.8–23 My ago) offers an opportunity to study past climate variability under high-CO2, warmer-than-present and the unipolar (Antarctic) glaciated state. Here, we present new high-resolution geochemical records from exquisitely well-preserved benthic foraminifera for the late Oligocene, an interval for which Antarctic ice-sheet size and stability are debated. Our records indicate four obliquity-paced glacial-interglacial cycles with ice-volume changes of up to ~70% of the modern Antarctic ice-sheet. The amplitude of ice-volume change during these late Oligocene glacial-interglacial cycles is comparable to that of the late Pliocene and early Pleistocene. Ice-volume estimates for interglacials are small enough to be accommodated by a land-based Antarctic ice-sheet but, for three of the four glacials studied, our calculations imply that ice sheets likely advanced beyond the Antarctic coastline onto the shelves. Our findings suggest an Antarctic ice-sheet vulnerable to melting driven by both bottom-up (ocean) and top-down (atmospheric) warming under late Oligocene warmer-than-present climate conditions

Paleomagnetic analysis of the Oligocene to early Miocene sediments of IODP SIte 342-U1406

Fine-grained magnetic particles in deep-sea sediments often statistically align with the ambient magnetic field during (and shortly after) deposition and can therefore record geomagnetic reversals. Correlation of these reversals to a geomagnetic polarity time scale is an important geochronological tool that facilitates precise stratigraphic correlation and dating of geological records globally. Sediments often carry a remanence strong enough for confident identification of polarity reversals, but in some cases a low signal-to-noise ratio prevents the construction of a reliable and robust magnetostratigraphy. Here we implement a data-filtering protocol, which can be integrated with the UPmag software package, to automatically reduce the maximum angular deviation and statistically mask noisy data and outliers deemed unsuitable for magnetostratigraphic interpretation. This protocol thus extracts a clearer signal from weakly magnetized sediments recovered at Integrated Ocean Drilling Program (IODP) Expedition 342 Site U1406 (Newfoundland margin, northwest Atlantic Ocean). The resulting magnetostratigraphy, in combination with shipboard and shore-based biostratigraphy, provides an age model for the study interval from IODP Site U1406 between Chrons C6Ar and C9n (~21–27 Ma). We identify rarely observed geomagnetic directional changes within Chrons C6Br, C7r, and C7Ar, and perhaps within Subchron C8n.1n. Our magnetostratigraphy dates three intervals of unusual stratigraphic behavior within the sediment drifts at IODP Site U1406 on the Newfoundland margin. These lithostratigraphic changes are broadly concurrent with the coldest climatic phases of the middle Oligocene to early Miocene and we hypothesize that they reflect changes in bottom water circulation