Samuel G. Rodriques's research while affiliated with Massachusetts Institute of Technology and other places
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Publications (11)
Current approaches to single-cell RNA sequencing (RNA-seq) provide only limited information about the dynamics of gene expression. Here we present RNA timestamps, a method for inferring the age of individual RNAs in RNA-seq data by exploiting RNA editing. To introduce timestamps, we tag RNA with a reporter motif consisting of multiple MS2 binding s...
Significance
Gene expression is precisely controlled across human cell types to control cellular functions and phenotypes. Here we present a technology to quantify the level of expression of genes in single cells, which will help to understand how genes are regulated in each cell type in the human body. We demonstrate that this technology improves...
Single-cell quantification of RNAs is important for understanding cellular heterogeneity and gene regulation, yet current approaches suffer from low sensitivity for individual transcripts, limiting their utility for many applications. Here we present Hybridization of Probes to RNA for sequencing (HyPR-seq), a method to sensitively quantify the expr...
Transcriptional programs implemented by cells often consist of complex temporal features, but current approaches to single-cell RNA sequencing only provide limited information about the dynamics of gene expression. Here, we present RNA timestamps, a method for inferring the age of individual RNAs in a sequencing-based readout by leveraging RNA edit...
Gene expression at fine scale
Mapping gene expression at the single-cell level within tissues remains a technical challenge. Rodriques et al. developed a method called Slide-seq, whereby RNA was spatially resolved from tissue sections by transfer onto a surface covered with DNA-barcoded beads. Applying Slide-seq to regions of a mouse brain revealed...
A supporting data file is included in .mat format containing the NAAB affinities digitized from [1].
(MAT)
We propose and theoretically study an approach to massively parallel single molecule peptide sequencing, based on single molecule measurement of the kinetics of probe binding (Havranek, et al., 2013) to the N-termini of immobilized peptides. Unlike previous proposals, this method is robust to both weak and non-specific probe-target affinities, whic...
The spatial organization of cells in tissue has a profound influence on their function, yet a high-throughput, genome-wide readout of gene expression with cellular resolution is lacking. Here, we introduce Slide-seq, a highly scalable method that enables facile generation of large volumes of unbiased spatial transcriptomes with 10 µm spatial resolu...
Shrinking problems in 3D printing
Although a range of materials can now be fabricated using additive manufacturing techniques, these usually involve assembly of a series of stacked layers, which restricts three-dimensional (3D) geometry. Oran et al. developed a method to print a range of materials, including metals and semiconductors, inside a gel...
We introduce the design and theoretical analysis of a fiber-optic architecture for neural recording without contrast agents, which transduces neural electrical signals into a multiplexed optical readout. Our sensor design is inspired by electro-optic modulators, which modulate the refractive index of a waveguide by applying a voltage across an elec...
We introduce a fiber-optic architecture for neural recording without contrast
agents, and study its properties theoretically. Our sensor design is inspired
by electrooptic modulators, which modulate the refractive index of a waveguide
by applying an electric field across an electrooptic core material, and allows
recording of the activities of indiv...
Citations
... TAP-seq [84]), hybridization baits (e.g. HyPR-seq [87] or biotinylated hybridization baits [74]) or custom beads [88]. ...
... We found that overall normalized gene expression remained constant over the cell cycle while miRNA targeting events, as measured by global editing patterns, increased throughout the cell cycle from G1 to M (Fig. 3i). This is consistent with previous observations that miRNA repression is weakest in the G1 phase 42 , but the increase in editing could also represent accumulated miRNA targeting over the cell cycle that is then diluted by new transcription in the G1 phase 43,44 . While transcripts with longer half-lives tend to accumulate slightly more editing events than do shorter-lived transcripts ( Supplementary Fig. 9), both groups display similarly increased editing throughout the cell cycle ( Supplementary Fig. 10), lending some evidence to the former hypothesis that genuine increased miRNA repression is involved. ...
... Because TRIBE represents a proximity approach to editing, the location of the cis-editing sites correlates with the location of RBP binding, but does not provide the exact nucleotides for RBP binding as does CLIP. Additional applications of MS2-TRIBE are being developed; for instance, MS2based RNA editing within single cells (Rodriques et al., 2020) provides a way to interrogate mRNA age by assessing the increase of edits with time and may be used to determine how cis-editing sites evolve with changes in developmental state. ...
... Optimal stLearn performance is achieved, however, when tissue morphology information from an H&E image (or other stain) is also included. That said, even without such imaging data, e.g. as with Slide-seq 15 , MERFISH 14 , seqFISH 13 and sci-Space data 33 , stLearn is still able to accurately infer spatial trajectories and cell-cell interactions based on spatial data and gene expression information alone. ...
... As a workaround for these challenges, multiple groups have proposed protein fingerprinting, in which partial sequence information is used to generate a unique protein fingerprint. [16][17][18][19][20] By mapping this fingerprint against a reference database, a protein can be identified. Thus far, proof-of-concept studies for protein fingerprinting have been limited to small model peptides, 19,[21][22][23] as their feasibility for fulllength protein is often hampered by their resolution, throughput or experimental complexity. ...
... On top of these, a thin tissue section is placed, and the cellular mRNA hybridizes to the primers. After sequencing the cellular mRNA content, it can be mapped back in space to the original tissue, as well as analysed with classical clustering methods (Ståhl et al., 2016;Rodriques et al., 2019). Additional to these experimental methods, various computational approaches facilitate the spatial reconstruction of scRNA-seq data (Nitzan et al., 2019;Stuart et al., 2019;Kleshchevnikov et al., 2020). ...
... Photo-patterning of materials is widely used for top-down fabrication. [36,52,68,69,83,137,[141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157] We achieved light-triggered outof-equilibrium patterning of an SDN hydrogel comprising photo-responsive peptide-type and lipid-type hydrogelators by inducing reaction-diffusion and seed-driven fiber formation (Figure 12a). [83] This out-of-equilibrium patterning proceeds through the spatial condensation of peptide-type nanofibers in the photo-irradiated areas and concurrent nanofiber depletion in the nonirradiated areas. ...
... Using optics to observe changes in cell refractive index and birefringence during electrical excitation [34] has failed to materialise as mainstream techniques. Theoretical studies have explored the feasibility of optical fibre refractometry [35] and surface plasmon resonance has been reported for neural recording in chamber [36] and fibre tip [37] configurations, but several issues remain unaddressed, including refractometry sensor characterisation, poor signal resolution, and a means of calibrating the outputted signal to biopotentials. Here, we present a practical implementation and experimental validation of a sensing fluorophore-free optrode with properties suitable for electrophysiology and brain-machine interface applications based on photonic techniques. ...