Quantifying T- and B-cell immune receptor distribution diversity to uncover their clinical relevance in clear cell renal cell carcinoma

Immune-modulating systemic therapies are often used to treat metastatic clear cell renal cell carcinoma (ccRCC). Used alone, sequence-based biomarkers neither accurately capture patient dynamics nor the tumor-immune microenvironment. To better understand the tumor ecology of this immune microenvironment, we used complementarity determining region-3 (CDR3) sequence recovery counts of the tumor infiltrating lymphocytes, and quantified tumor infiltration by sequences recovered from patient tumors by applying a generalized diversity index (GDI) to CDR3 sequence distributions across two distinct ccRCC cohorts. GDI can be understood as a curve over a continuum of diversity scales and allows sensitive characterization of distributions to capture richness, evenness, and subsampling uncertainty, along with other important metrics. For example, richness quantifies the total unique sequence count, while evenness quantifies similarities across sequence frequencies. We observed significant differences in receptor sequence diversity across gender and race. Further, our analysis revealed that patients with larger and more clinically aggressive tumors had increased richness of recovered tumoral CDR3 sequences, specifically in those from T-cell receptor alpha and B-cell immunoglobulin lambda light chain. We identified a novel and robust measure of distribution evenness, using GDI's inflection point (IP). High IP values associated with improved overall survival, suggesting that normal-like sequence distributions lead to better outcomes. Our results propose a new quantitative tool that can be used to better characterize patient-level differences related to immune cell infiltration and, can be used to identify unique characteristics of tumor-infiltrating lymphocyte heterogeneity in ccRCC and other malignancies.

Syndiospecific coordination (Co)polymerization of carbazole-substituted styrene derivatives using the scandium catalyst system

Perfect syndiospecific polymerization of carbazole-substituted styrene derivatives was achieved using a rare-earth metal catalyst. Also copolymerization of FSt with styrene afforded copolymers with gradient sequence distributions and easily tunable incorporation rate.

Patterning Polyelectrolyte Complexes with Alternating Monomer Sequence Distributions

<div> <div> <div> <p>Charge-driven complexation of polyelectrolytes in water is a fundamental phase separation phenomenon that is prevalent in nature and across the high-value technology landscape. Here we describe an experimentally convenient and versatile approach to construct patterned PECs, comprising well-defined charged macromolecules with both ionic styrene and neutral maleimide units alternating in the chain sequence. </p> </div> </div> </div>

Patterning Polyelectrolyte Complexes with Alternating Monomer Sequence Distributions

<div> <div> <div> <p>Charge-driven complexation of polyelectrolytes in water is a fundamental phase separation phenomenon that is prevalent in nature and across the high-value technology landscape. Here we describe an experimentally convenient and versatile approach to construct patterned PECs, comprising well-defined charged macromolecules with both ionic styrene and neutral maleimide units alternating in the chain sequence. </p> </div> </div> </div>

Deep generative models for T cell receptor protein sequences

Probabilistic models of adaptive immune repertoire sequence distributions can be used to infer the expansion of immune cells in response to stimulus, differentiate genetic from environmental factors that determine repertoire sharing, and evaluate the suitability of various target immune sequences for stimulation via vaccination. Classically, these models are defined in terms of a probabilistic V(D)J recombination model which is sometimes combined with a selection model. In this paper we take a different approach, fitting variational autoencoder (VAE) models parameterized by deep neural networks to T cell receptor (TCR) repertoires. We show that simple VAE models can perform accurate cohort frequency estimation, learn the rules of VDJ recombination, and generalize well to unseen sequences. Further, we demonstrate that VAE-like models can distinguish between real sequences and sequences generated according to a recombination-selection model, and that many characteristics of VAE-generated sequences are similar to those of real sequences.

Sequence controlled copolymerization of lactide and a functional cyclic carbonate using stereoselective aluminum catalysts

Stereoselective aluminum complexes were applied for the ROP of LA and MAC producing functional copolyesters with quasi-diblock, tapered, gradient and random sequence distributions.