Evaluation and comparison of multi-omics data integration methods for cancer subtyping

Computational integrative analysis has become a significant approach in the data-driven exploration of biological problems. Many integration methods for cancer subtyping have been proposed, but evaluating these methods has become a complicated problem due to the lack of gold standards. Moreover, questions of practical importance remain to be addressed regarding the impact of selecting appropriate data types and combinations on the performance of integrative studies. Here, we constructed three classes of benchmarking datasets of nine cancers in TCGA by considering all the eleven combinations of four multi-omics data types. Using these datasets, we conducted a comprehensive evaluation of ten representative integration methods for cancer subtyping in terms of accuracy measured by combining both clustering accuracy and clinical significance, robustness, and computational efficiency. We subsequently investigated the influence of different omics data on cancer subtyping and the effectiveness of their combinations. Refuting the widely held intuition that incorporating more types of omics data always produces better results, our analyses showed that there are situations where integrating more omics data negatively impacts the performance of integration methods. Our analyses also suggested several effective combinations for most cancers under our studies, which may be of particular interest to researchers in omics data analysis.

The Ever-Expanding Pseudomonas Genus: Description of 43 New Species and Partition of the Pseudomonas Putida Group

The genus Pseudomonas hosts an extensive genetic diversity and is one of the largest genera among Gram-negative bacteria. Type strains of Pseudomonas are well-known to represent only a small fraction of this diversity and the number of available Pseudomonas genome sequences is increasing rapidly. Consequently, new Pseudomonas species are regularly reported and the number of species within the genus is in constant evolution. In this study, whole genome se-quencing enabled us to define 43 new Pseudomonas species and to provide an update of the Pseu-domonas evolutionary and taxonomic relationships. Phylogenies based on the rpoD gene and whole genome sequences, including 316 and 313 type strains of Pseudomonas, respectively, re-vealed sixteen groups of Pseudomonas and justified the partitioning of the P. putida group into fifteen subgroups. Pairwise average nucleotide identities were calculated between type strains and a selection of 60 genomes of non-type strains of Pseudomonas. Forty-one strains were incor-rectly assigned at the species level and among those, 19 strains were shown to represent an addi-tional 13 new Pseudomonas species that remain to be formally classified. This work pinpoints the importance of correct taxonomic assignment and phylogenetic classification in order to perform integrative studies linking genetic diversity, lifestyle and metabolic potential of Pseudomonas spp.

The integrative biology of pigment organelles, a quantum chemical approach

Coloration is a complex phenotypic trait involving both physical and chemical processes at a multiscale level, from molecules to tissues. Pigments, whose main property is to absorb specific wavelengths of visible light, are usually deposited in specialized organelles or complex matrices comprising proteins, metals, ions and redox compounds, among others. By modulating electronic properties and stability, interactions between pigments and these molecular actors can lead to color tuning. Furthermore, pigments are not only important for visual effects but also provide other critical functions, such as detoxification and antiradical activity. Hence, integrative studies of pigment organelles are required to understand how pigments interact with their cellular environment. In this review, we show how quantum chemistry, a computational method that models the molecular and optical properties of pigments, has provided key insights into the mechanisms by which pigment properties, from color to reactivity, are modulated by their organellar environment. These results allow to rationalize and to predict the way pigments behave in supramolecular complexes, up to the complete modelling of pigment organelles. We also discuss the main limitations of quantum chemistry, emphasizing the need for carrying experimental work with identical vigor. We finally suggest that taking into account the ecology of pigments (i.e. how they interact with these various other cellular components and at higher organizational levels) will lead to a greater understanding of how and why animals are vividly and variably colored, two fundamental questions in organismal biology.

Systematic redescription of Solen (Ensisolen) tehuelchus and Ensis macha (Bivalvia: Solenoidea) from Argentina, southwestern Atlantic Ocean

In the present study, bivalves belonging to the superfamily Solenoidea that inhabit the Argentinean Sea are redescribed. The specimens studied in this work were collected by scuba diving in the Gulf of San José, Argentina. Additional specimens from different malacological collections were revised to update the geographical distribution of valid species. According to the literature, there exist two species for the “Argentinean” and “Magellan” biogeographical provinces. However, ten nominal taxa, with uncertain taxonomic status, have been mentioned for the study area. Field work, local collection survey and type material examination allow confirming two valid species: Solen (Ensisolen) tehuelchus Hanley (Solenidae) and Ensis macha (Molina) (Pharidae). A morphological comparison between S. tehuelchus and S. gaudichaudi Chenu and S. obliqua Spengler is provided as well type locality, repository and synonymy list. The type material of all related species are illustrated whenever possible. Establishing the valid names of these species is the first step towards more integrative studies including genetic and zoogeographical analyses.

Plant Metabolites Involved in the Differential Development of a Heliantheae-Specialist Insect

Balanced nutritional intake is essential to ensure that insects undergo adequate larval development and metamorphosis. Integrative multidisciplinary approaches have contributed valuable insights regarding the ecological and evolutionary outcomes of plant–insect interactions. To address the plant metabolites involved in the larval development of a specialist insect, we investigated the development of Chlosyne lacinia caterpillars fed on Heliantheae species (Tithonia diversifolia, Tridax procumbens and Aldama robusta) leaves and determined the chemical profile of plants and insects using a metabolomic approach. By means of LC-MS and GC-MS combined analyses, 51 metabolites were putatively identified in Heliantheae species and C. lacinia caterpillars and frass; these metabolites included flavonoids, sesquiterpene lactones, monoterpenoids, sesquiterpenoids, diterpenes, triterpenes, oxygenated terpene derivatives, steroids and lipid derivatives. The leading discriminant metabolites were diterpenes, which were detected only in A. robusta leaves and insects that were fed on this plant-based diet. Additionally, caterpillars fed on A. robusta leaves took longer to complete their development to the adult phase and exhibited a greater diapause rate. Hence, we hypothesized that diterpenes may be involved in the differential larval development. Our findings shed light on the plant metabolites that play roles in insect development and metabolism, opening new research avenues for integrative studies of insect nutritional ecology.

Molecular and morphological revision of small Myotinae from the Himalayas shed new light on the poorly known genus Submyotodon (Chiroptera: Vespertilionidae)

The systematics status of the constituent species of the M. mystacinus morphogroup in the Himalayan region has long been marred by uncertainty. Lack of integrative studies combining morphological and genetic data from specimens recently collected in this region has hampered our understanding of cryptic variations in this complex taxonomic group. To address this issue, new material from the Himalayan region of India and Nepal was obtained and vouchered specimens in the holdings of various museums were also re-examined. As comparative material, a large series of relevant specimens from South and Southeast Asia were also included in this revision. Using a combination of multivariate analysis of craniodental characters and molecular reconstructions, we critically evaluated the systematic position of the small Myotinae in the Himalayas. We establish that M. nipalensis forms a very distinct lineage (which also includes the recently described M. annatessae) and refute previous taxonomic suggestions that it is related to M. davidii. Our study also conclusively proved the common occurrence of the poorly known genus Submyotodon in the Himalayan region (Afghanistan, Pakistan, India, Nepal and China) and evidenced species-level divergences within that genus. Submyotodon species share nyctalodont or semi-nyctalodont lower molar configuration with few other small and unrelated Myotinae from Asia suggesting that these unusual dental characters are homoplasious in this subfamily. We also noticed a very confused taxonomic situation associated with many DNA sequences of Asian Myotis deposited in public repositories and call for possibilities of better data curation.

The Role of Buddhist Studies in Fostering Metadisciplinary Conversations and Improving Pedagogical Collaborations

Buddhist studies has been at the center of a number of pedagogical experiments that have emerged on my campus over the last five years in response to Penn State University’s general education reform introducing an integrative studies requirement. The first half of this paper introduces two of these interdisciplinary collaborations. I discuss the structure and goals of these two courses and detail how I integrated Buddhist Studies into the design of each. In the second half of the paper, I describe how the practice of what I call “metadisciplinarity” can help to avoid some of the pitfalls commonly faced in interdisciplinary collaborations. I discuss both how to engage in metadisciplinary reflection and communication and the strengths that Buddhist studies scholars can bring to this kind of pedagogical collaboration based on some core features of our field.

Avian Diversity: Speciation, Macroevolution, and Ecological Function

The origin, distribution, and function of biological diversity are fundamental themes of ecology and evolutionary biology. Research on birds has played a major role in the history and development of these ideas, yet progress was for many decades limited by a focus on patterns of current diversity, often restricted to particular clades or regions. Deeper insight is now emerging from a recent wave of integrative studies combining comprehensive phylogenetic, environmental, and functional trait data at unprecedented scales. We review these empirical advances and describe how they are reshaping our understanding of global patterns of bird diversity and the processes by which it arises, with implications for avian biogeography and functional ecology. Further expansion and integration of data sets may help to resolve longstanding debates about the evolutionary origins of biodiversity and offer a framework for understanding and predicting the response of ecosystems to environmental change.

Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin

The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca2+in nonmuscle cells. Here we report the mechanism of Ca2+-mediated regulation ofEntamoeba histolyticaα-actinin-2 (EhActn2) with features expected for the common ancestor ofEntamoebaand higher eukaryotic α-actinins. Crystal structures of Ca2+-free and Ca2+-boundEhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of theEhActn2 CaMD for Ca2+, binding of which can only be regulated in the presence of physiological concentrations of Mg2+. Ca2+binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover thatEhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery.

Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations

Nanodiscs are membrane mimetics that consist of a protein belt surrounding a lipid bilayer, and are broadly used for characterization of membrane proteins. Here, we investigate the structure, dynamics and biophysical properties of two small nanodiscs, MSP1D1ΔH5 and ΔH4H5. We combine our SAXS and SANS experiments with molecular dynamics simulations and previously obtained NMR and EPR data to derive and validate a conformational ensemble that represents the structure and dynamics of the nanodisc. We find that it displays conformational heterogeneity with various elliptical shapes, and with substantial differences in lipid ordering in the centre and rim of the discs. Together, our results reconcile previous apparently conflicting observations about the shape of nanodiscs, and pave the way for future integrative studies of larger complex systems such as membrane proteins embedded in nanodiscs.