Adaptive Bayesian variable clustering via structural learning of breast cancer data.

The clustering of proteins is of interest in cancer cell biology. This article proposes a hierarchical Bayesian model for protein (variable) clustering hinging on correlation structure. Starting from a multivariate normal likelihood, we enforce the clustering through prior modeling using angle-based unconstrained reparameterization of correlations and assume a truncated Poisson distribution (to penalize a large number of clusters) as prior on the number of clusters.

Circadian Gene Selection for Time-to-event Phenotype by Integrating CNV and RNAseq Data.

Background: The endogenous circadian clock, which controls daily rhythms in the expression of at least half of the mammalian genome, has a major influence on cell physiology. Consequently, disruption of the circadian system is associated with wide range of diseases including cancer. While several circadian clock genes have been associated with cancer progression, little is known about the survival when two or more platforms are considered together.

Bayesian Criterion Based Variable Selection.

Bayesian approaches for criterion based selection include the marginal likelihood based highest posterior model (HPM) and the deviance information criterion (DIC). The DIC is popular in practice as it can often be estimated from sampling based methods with relative ease and DIC is readily available in various Bayesian software. We find that sensitivity of DIC based selection can be high, in the range of 90 - 100%.

Integration of Survival and Binary Data for Variable Selection and Prediction: A Bayesian Approach.

We consider the problem where the data consist of a survival time and a binary outcome measurement for each individual, as well as corresponding predictors. The goal is to select the common set of predictors which affect both the responses, and not just only one of them. In addition, we develop a survival prediction model based on data integration.

A Dinickel Catalyzed Cyclopropanation without the Formation of a Metal Carbene Intermediate.

(NDI)Ni catalysts (NDI=naphthyridine-diimine) promote cyclopropanation reactions of 1,3-dienes using (Me Si)CHN . Mechanistic studies reveal that a metal carbene intermediate is not part of the catalytic cycle. The (NDI)Ni (CHSiMe ) complex was independently synthesized and found to be unreactive toward dienes.

Bayesian structural equation modeling in multiple omics data with application to circadian genes.

Motivation: It is well known that the integration among different data-sources is reliable because of its potential of unveiling new functionalities of the genomic expressions, which might be dormant in a single-source analysis. Moreover, different studies have justified the more powerful analyses of multi-platform data. Toward this, in this study, we consider the circadian genes' omics profile, such as copy number changes and RNA-sequence data along with their survival response.

Multiple Omics Data Integration to Identify Long Noncoding RNA Responsible for Breast Cancer-Related Mortality.

Long non-coding RNAs (lncRNAs) are a large and diverse class of transcribed RNAs, which have been shown to play a significant role in developing cancer. In this study, we apply integrative modeling framework to integrate the DNA copy number variation (CNV), lncRNA expression, and downstream target protein expression to predict patient survival in breast cancer. We develop a 3-stage model combining a mechanical model (lncRNA regressed on CNV and target proteins regressed on lncRNA) and a clinical model (survival regressed on estimated effects from the mechanical models).

Bayesian data integration and variable selection for pan-cancer survival prediction using protein expression data.

Accurate prognostic prediction using molecular information is a challenging area of research, which is essential to develop precision medicine. In this paper, we develop translational models to identify major actionable proteins that are associated with clinical outcomes, like the survival time of patients. There are considerable statistical and computational challenges due to the large dimension of the problems.

Carbene Formation and Transfer at a Dinickel Active Site.

The synthesis and reactivity of a dinickel bridging carbene is described. The previously reported [ NDI]Ni(CH) complex (NDI = naphthyridine-diimine) reacts with PhCN to generate a metastable diazoalkane adduct, which eliminates N at 60 °C to yield a paramagnetic Ni(μ-CPh) complex. The Ni(μ-CPh) complex undergoes carbene transfer to -BuNC via an initial isonitrile adduct, which, upon heating, releases free -BuNCCPh.

A Terminal Iron(IV) Nitride Supported by a Super Bulky Guanidinate Ligand and Examination of Its Electronic Structure and Reactivity.

Utilizing the bulky guanidinate ligand [L] (L = (Ar*N)C(R), Ar* = 2,6-bis(diphenylmethyl)-4-tert-butylphenyl, R = NCBu) for kinetic stabilization, the synthesis of a rare terminal Fe(IV) nitride complex is reported. UV irradiation of a pyridine solution of the Fe(II) azide [L]FeN(py) (3-py) at 0 °C cleanly generates the Fe(IV) nitride [L]FeN(py) (1). The N NMR spectrum of the 1 (50% Fe≡N) isotopomer shows a resonance at 1016 ppm (vs externally referenced CHNO at 380 ppm), comparable to that known for other terminal iron nitrides.

Donor Properties of a New Class of Guanidinate Ligands Possessing Ketimine Backbones: A Comparative Study Using Iron.

Addition of 1 equiv of LiN═C(t)Bu2 or LiN═Ad (Ad = 2-adamantyl) to the aryl carbodiimide C(NDipp)2 (Dipp = 2,6-diisopropylphenyl) readily generates the lithium ketimine-guanidinates Li(THF)2[(X)C(NDipp)2] (X = N═C(t)Bu2 (1-(t)Bu), N═Ad (1-Ad)) in excellent yields. These new ligands can be readily metalated with iron to give the N,N'-bidentate chelates [{(X)C(NDipp)2}FeBr]2 (X = N═C(t)Bu2 (5-(t)Bu), N═Ad (5-Ad)), in which the ketimines behave as noncoordinating backbone substituents. In an effort to understand the potential electronic contributions of the ketimine group to the ligand architecture, a thorough structural and electronic study was conducted comparing the features and properties of 5-(t)Bu and 5-Ad to their guanidinate and amidinate analogues [{(X)C(NDipp)2}FeBr]2 (X = (i)Pr2N (6), (t)Bu (7)).

Synthesis of a "super bulky" guanidinate possessing an expandable coordination pocket.

Friedel-Crafts alkylation of 4-tert-butylaniline with 2 equiv of benzhydrol affords bulky 2,6-bis(diphenylmethyl)-4-tert-butylaniline (Ar*NH2) in good yield, which can be readily synthesized on a tens of grams scale. The reaction of 6 equiv of Ar*NH2 with triphosgene generates the symmetric urea (Ar*NH)2CO, which, upon dehydration with a P2O5/Al2O3 slurry in pyridine, produces the sterically encumbered carbodiimide (Ar*N)2C as an air-stable white solid. The treatment of (Ar*N)2C with LiN═C(t)Bu2 in tetrahydrofuran cleanly gives the monomeric lithium guanidinate Li[(Ar)*ketguan], free of coordinating solvent, in 85% yield.

A multimetallic piano-stool Ir-Sn3 catalyst for nucleophilic substitution reaction of γ-hydroxy lactams through N-acyliminium ions.

A multimetallic piano-stool complex [Cp*Ir(SnCl(3))(2){SnCl(2)(H(2)O)(2)}] (1) having Ir-Sn(3) motif has been synthesized from [Cp*IrCl(2)](2) and SnCl(2). The multimetallic complex catalytically promotes the nucleophilic substitution reaction (here after α-amidoalkylation reaction) of γ-hydroxylactams generated from phthalimidals to obtain decorated isoindolinones in excellent yields. Succinamidals, however, lead to the substituted pyrrolidinones (thermodynamic control product) via S(N)1-type path as well as eliminated pyrrolinones (kinetic control product) via an E1-type path, depending on the reaction parameters.