Biology subjects

Bo Li

Publications and source records attributed to Bo Li.

5 recordsLinked to original sources

bioRxiv2020

Metabolic features of mouse and human retinas: rods vs. cones, macula vs. periphery, retina vs. RPE

Photoreceptors, especially cones, which are enriched in the human macula, have high energy demands, making them vulnerable to metabolic stress. Metabolic dysfunction of photoreceptors and their supporting retinal pigment epithelium (RPE) is an important underlying cause of degenerative retinal diseases. However, how cones and the macula support their exorbitant metabolic demand and communicate with RPE is unclear. By profiling metabolite uptake and release and analyzing metabolic genes, we have found cone-rich retinas and human macula share specific metabolic features with upregulated pathways in pyruvate metabolism, mitochondrial TCA cycle and lipid synthesis. Human neural retina and RPE have distinct but complementary metabolic features. Retinal metabolism centers on NADH production and neurotransmitter biosynthesis. The retina needs aspartate to sustain its aerobic glycolysis and mitochondrial metabolism. RPE metabolism is directed toward NADPH production and biosynthesis of acetyl-rich metabolites, serine and others. RPE consumes multiple nutrients, including proline, to produce metabolites for the retina.

neuroscience↗

bioRxiv2016

Ultrasensitive detection of TCR hypervariable region in solid-tissue RNA-seq data

Characterization of tissue-infiltrating T cell repertoire is critical to understanding tumor-immune interactions and autoimmune disease etiology. We present TRUST, an open source algorithm for calling the TCR transcript hypervariable CDR3 regions using unselected RNA-seq data profiled from solid tissues. TRUST achieved high sensitivity in CDR3 calling even for samples with low sequencing depth and has demonstrated utilities in its application to large tumor cohorts.

Bioinformatics↗

bioRxiv2016

Prober: A general toolkit for analyzing sequencing-based ‘toeprinting’ assays

A number of high-throughput transcriptase drop-off assays have recently been developed to probe post-transcriptional dynamics of RNA-protein interaction, RNA structure, and post-transcriptional modifications. Although these assays survey a diverse set of epitranscriptomic marks, they share methodological similarities and as such their interpretation is predicated on addressing similar computational challenges. Among these, a key question is how to learn isoform-specific chemical modification profiles in the face of complex read multi-mapping. In this paper, we propose PROBer, the first rigorous statistical model to handle these challenges for a general set of sequencing-based toeprinting assays.

Genomics↗

bioRxiv2016

Parvalbumin interneuron dysfunction in a thalamus - prefrontal cortex circuit in Disc1 deficiency mice

Two of the most consistent findings across disrupted-in-schizophrenia-1 (DISC1) mouse models are impaired working memory and reduced number or function of parvalbumin interneurons within the prefrontal cortex. While these findings suggest parvalbumin interneuron dysfunction in DISC1-related pathophysiology, to date, cortical inhibitory circuit function has not been investigated in depth in DISC1 deficiency mouse models. Here we assessed the function of a feedforward circuit between the mediodorsal thalamus (MD) and the medial prefrontal cortex (mPFC) in mice harboring a deletion in one allele of the Disc1 gene. We found that the inhibitory drive onto layer 3 pyramidal neurons in the mPFC was significantly reduced in the Disc1 deficient mice. This reduced inhibition was accompanied by decreased GABA release from local parvalbumin, but not somatostatin, inhibitory interneurons, and by impaired feedforward inhibition in the MD-mPFC circuit. Our results reveal a cellular mechanism by which deficiency in DISC1 causes neural circuit dysfunction frequently implicated in psychiatric disorders.

Neuroscience↗

bioRxiv2014

Evaluation of de novo transcriptome assemblies from RNA-Seq data

De novo RNA-Seq assembly facilitates the study of transcriptomes for species without sequenced genomes, but it is challenging to select the most accurate assembly in this context. To address this challenge, we developed a model-based score, RSEM-EVAL, for evaluating assemblies when the ground truth is unknown. Our experiments show that RSEM-EVAL correctly reflects assembly accuracy, as measured by REF-EVAL, a refined set of ground-truth-based scores that we also developed. With the guidance of RSEM-EVAL, we assembled the transcriptome of the regenerating axolotl limb; this assembly compares favorably to a previous assembly.

Bioinformatics↗