搜索结果：CRISPR gene editing

Essential genes constitute the core of genes which cannot be mutated too much nor lost along the evolutionary history of a species. Natural selection is expected to be stricter on essential genes and on conserved (highly shared) genes, than on genes that are either nonessential or peculiar to a single or a few species. In order to further assess this expectation, we study here how essentiality of a gene is connected with its degree of conservation among several unrelated bacterial species, each one characterised by its own codon usage bias. Confirming previous results on E. coli, we show the existence of a universal exponential relation between gene essentiality and conservation in bacteria. Moreover we show that, within each bacterial genome, there are at least two groups of functionally distinct genes, characterised by different levels of conservation and codon bias: i) a core of essential genes, mainly related to cellular information processing; ii) a set of less conserved nonessential genes with prevalent functions related to metabolism. In particular, the genes in the first group are more retained among species, are subject to a stronger purifying conservative selection and di

Image editing aims to edit the given synthetic or real image to meet the specific requirements from users. It is widely studied in recent years as a promising and challenging field of Artificial Intelligence Generative Content (AIGC). Recent significant advancement in this field is based on the development of text-to-image (T2I) diffusion models, which generate images according to text prompts. These models demonstrate remarkable generative capabilities and have become widely used tools for image editing. T2I-based image editing methods significantly enhance editing performance and offer a user-friendly interface for modifying content guided by multimodal inputs. In this survey, we provide a comprehensive review of multimodal-guided image editing techniques that leverage T2I diffusion models. First, we define the scope of image editing from a holistic perspective and detail various control signals and editing scenarios. We then propose a unified framework to formalize the editing process, categorizing it into two primary algorithm families. This framework offers a design space for users to achieve specific goals. Subsequently, we present an in-depth analysis of each component withi

Recent advancements in diffusion models have shown remarkable proficiency in editing 2D images based on text prompts. However, extending these techniques to edit scenes in Neural Radiance Fields (NeRF) is complex, as editing individual 2D frames can result in inconsistencies across multiple views. Our crucial insight is that a NeRF scene's geometry can serve as a bridge to integrate these 2D edits. Utilizing this geometry, we employ a depth-conditioned ControlNet to enhance the coherence of each 2D image modification. Moreover, we introduce an inpainting approach that leverages the depth information of NeRF scenes to distribute 2D edits across different images, ensuring robustness against errors and resampling challenges. Our results reveal that this methodology achieves more consistent, lifelike, and detailed edits than existing leading methods for text-driven NeRF scene editing.

Even the largest neural networks make errors, and once-correct predictions can become invalid as the world changes. Model editors make local updates to the behavior of base (pre-trained) models to inject updated knowledge or correct undesirable behaviors. Existing model editors have shown promise, but also suffer from insufficient expressiveness: they struggle to accurately model an edit's intended scope (examples affected by the edit), leading to inaccurate predictions for test inputs loosely related to the edit, and they often fail altogether after many edits. As a higher-capacity alternative, we propose Semi-Parametric Editing with a Retrieval-Augmented Counterfactual Model (SERAC), which stores edits in an explicit memory and learns to reason over them to modulate the base model's predictions as needed. To enable more rigorous evaluation of model editors, we introduce three challenging language model editing problems based on question answering, fact-checking, and dialogue generation. We find that only SERAC achieves high performance on all three problems, consistently outperforming existing approaches to model editing by a significant margin. Code, data, and additional project

Large-scale text-to-image diffusion models achieve unprecedented success in image generation and editing. However, how to extend such success to video editing is unclear. Recent initial attempts at video editing require significant text-to-video data and computation resources for training, which is often not accessible. In this work, we propose vid2vid-zero, a simple yet effective method for zero-shot video editing. Our vid2vid-zero leverages off-the-shelf image diffusion models, and doesn't require training on any video. At the core of our method is a null-text inversion module for text-to-video alignment, a cross-frame modeling module for temporal consistency, and a spatial regularization module for fidelity to the original video. Without any training, we leverage the dynamic nature of the attention mechanism to enable bi-directional temporal modeling at test time. Experiments and analyses show promising results in editing attributes, subjects, places, etc., in real-world videos. Code is made available at \url{https://github.com/baaivision/vid2vid-zero}.

CRISPR/Cas has the potential to revolutionize medicine, agriculture, and biology. Understanding the trajectory of CRISPR research, how it is influenced and who pays for it, is an essential research policy question. We use a combination of methods to map, via quantitative content analysis of CRISPR papers, the research funding profile of major government agencies and organizations philanthropic, and the networks involved in supporting key stages of high-influence research, namely basic biological research and technological development. The results of the content analysis show how the research supported by the main US government agencies focus both on the study of CRISPR as a biological phenomenon and on its technological development and use as a biomedical research tool. US philanthropic organizations with the exception of HHMI, tend, by contrast, to specialize in funding CRISPR as a genome editing technology. We present a model of co-funding networks at the two most prominent institutions for CRISPR/Cas research, the University of California and the Harvard/MIT/Broad Institute, to illuminate how philanthropic organizations have articulated with government agencies to co-finance the

CRISPR genome engineering and single-cell RNA sequencing have accelerated biological discovery. Single-cell CRISPR screens unite these two technologies, linking genetic perturbations in individual cells to changes in gene expression and illuminating regulatory networks underlying diseases. Despite their promise, single-cell CRISPR screens present substantial statistical challenges. We demonstrate through theoretical and real data analyses that a standard method for estimation and inference in single-cell CRISPR screens -- "thresholded regression" -- exhibits attenuation bias and a bias-variance tradeoff as a function of an intrinsic, challenging-to-select tuning parameter. To overcome these difficulties, we introduce GLM-EIV ("GLM-based errors-in-variables"), a new method for single-cell CRISPR screen analysis. GLM-EIV extends the classical errors-in-variables model to responses and noisy predictors that are exponential family-distributed and potentially impacted by the same set of confounding variables. We develop a computational infrastructure to deploy GLM-EIV across hundreds of processors on clouds (e.g., Microsoft Azure) and high-performance clusters. Leveraging this infrastru

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), linked with CRISPR associated (CAS) genes, play a profound role in the interactions between phage and their bacterial hosts. It is now well understood that CRISPR-CAS systems can confer adaptive immunity against bacteriophage infections. However, the possibility of failure of CRISPR immunity may lead to a productive infection by the phage (cell lysis) or lysogeny. Recently, CRISPR-CAS genes have been implicated in changes to group behaviour, including biofilm formation, of the bacterium Pseudomonas aeruginosa when lysogenized. For lysogens with a CRISPR system, another recent experimental study suggests that bacteriophage re-infection of previously lysogenized bacteria may lead to cell death. Thus CRISPR immunity can have complex effects on phage-host-lysogen interactions, particularly in a biofilm. In this contribution, we develop and analyse a series of models to elucidate and disentangle these interactions. From a therapeutic standpoint, CRISPR immunity increases biofilm resistance to phage therapy. Our models predict that lysogens may be able to displace CRISPR-immune bacteria in a biofilm, and thus suggest str

Reconstructing the tree of life from molecular sequences is a fundamental problem in computational biology. Modern data sets often contain a large number of genes, which can complicate the reconstruction problem due to the fact that different genes may undergo different evolutionary histories. This is the case in particular in the presence of horizontal genetic transfer (HGT), where a gene is inherited from a distant species rather than an immediate ancestor. Such an event produces a gene tree which is distinct from, but related to, the species phylogeny. In previous work, a natural stochastic models of HGT was introduced and studied. It was shown, both in simulation and theoretical studies, that a species phylogeny can be reconstructed from gene trees despite surprisingly high rates of HGT under this model. Rigorous lower and upper bounds on this achievable rate were also obtained, but a large gap remained. Here we close this gap, up to a constant. Specifically we show that a species phylogeny can be reconstructed correctly from gene trees even when, on each gene, each edge of the species tree has a constant probability of being the location of an HGT event. Our new reconstruction

While large pre-trained models have enabled impressive results on a variety of downstream tasks, the largest existing models still make errors, and even accurate predictions may become outdated over time. Because detecting all such failures at training time is impossible, enabling both developers and end users of such models to correct inaccurate outputs while leaving the model otherwise intact is desirable. However, the distributed, black-box nature of the representations learned by large neural networks makes producing such targeted edits difficult. If presented with only a single problematic input and new desired output, fine-tuning approaches tend to overfit; other editing algorithms are either computationally infeasible or simply ineffective when applied to very large models. To enable easy post-hoc editing at scale, we propose Model Editor Networks using Gradient Decomposition (MEND), a collection of small auxiliary editing networks that use a single desired input-output pair to make fast, local edits to a pre-trained model's behavior. MEND learns to transform the gradient obtained by standard fine-tuning, using a low-rank decomposition of the gradient to make the parameteriz

Modelling gene regulatory networks not only requires a thorough understanding of the biological system depicted but also the ability to accurately represent this system from a mathematical perspective. Throughout this chapter, we aim to familiarise the reader with the biological processes and molecular factors at play in the process of gene expression regulation.We first describe the different interactions controlling each step of the expression process, from transcription to mRNA and protein decay. In the second section, we provide statistical tools to accurately represent this biological complexity in the form of mathematical models. Amongst other considerations, we discuss the topological properties of biological networks, the application of deterministic and stochastic frameworks and the quantitative modelling of regulation. We particularly focus on the use of such models for the simulation of expression data that can serve as a benchmark for the testing of network inference algorithms.

Comparing large covariance matrices has important applications in modern genomics, where scientists are often interested in understanding whether relationships (e.g., dependencies or co-regulations) among a large number of genes vary between different biological states. We propose a computationally fast procedure for testing the equality of two large covariance matrices when the dimensions of the covariance matrices are much larger than the sample sizes. A distinguishing feature of the new procedure is that it imposes no structural assumptions on the unknown covariance matrices. Hence the test is robust with respect to various complex dependence structures that frequently arise in genomics. We prove that the proposed procedure is asymptotically valid under weak moment conditions. As an interesting application, we derive a new gene clustering algorithm which shares the same nice property of avoiding restrictive structural assumptions for high-dimensional genomics data. Using an asthma gene expression dataset, we illustrate how the new test helps compare the covariance matrices of the genes across different gene sets/pathways between the disease group and the control group, and how t

As organisms are faced with intense rapidly changing selective pressures, new genetic material is required to facilitate adaptation. Among sources of genetic novelty, gene duplications and transposable elements (TEs) offer new genes or new regulatory patterns that can facilitate evolutionary change. With advances in genome sequencing it is possible to gain a broader view of how gene family proliferation and TE content evolve in non-model species when populations become threatened. Freshwater bivalves (Unionidae) currently face severe anthropogenic challenges. Over 70% of species in the United States are threatened, endangered or extinct due to pollution, damming of waterways, and overfishing. We have created a reference genome for M. nervosa to determine how genome content has evolved in the face of these widespread environmental challenges. We observe a burst of recent transposable element proliferation causing a 382 Mb expansion in genome content. Gene family expansion is common, with a duplication rate of 1.16 x 10^-8 per gene per generation. Cytochrome P450, ABC transporters, Hsp70 genes, von Willebrand proteins, chitin metabolism genes, mitochondria eating proteins, and opsin

CRISPR systems experience off-target effects that interfere with the ability to accurately perform genetic edits. While empirical models predict off-target effects in specific platforms, there is a gap for a wide-ranging mechanistic model of CRISPR systems based on evidence from the essential processes of target recognition. In this work, we present a first principles model supported by many experiments performed in vivo and in vitro. First, we observe and model the conformational changes and discrete stepped DNA unwinding events of SpCas9-CRISPR target recognition process in a cell-free transcription-translation system using truncated guide RNAs, confirming structural and FRET microscopy experiments. Second, we implement an energy landscape to describe single mismatch effects observed in vivo for spCas9 and Cas12a CRISPR systems. From the mismatch analysis results we uncover that CRISPR class 2 systems maintain their kinetic proofreading mechanism by utilizing intermittent energetic barriers and we show how to leverage the landscape to improve target specificity.

Clustered regularly interspaced short palindromic repeats (CRISPR) in bacterial and archaeal DNA have recently been shown to be a new type of anti-viral immune system in these organisms. We here study the diversity of spacers in CRISPR under selective pressure. We propose a population dynamics model that explains the biological observation that the leader-proximal end of CRISPR is more diversified and the leader-distal end of CRISPR is more conserved. This result is shown to be in agreement with recent experiments. Our results show thatthe CRISPR spacer structure is influenced by and provides a record of the viral challenges that bacteria face.

RNA-guided gene editing based on the CRISPR-Cas system is currently the most effective genome editing technique. Here, we report that the SviCas3 from the subtype I-B-Svi Cas system in Streptomyces virginiae IBL14 is an RNA-guided and DNA-guided DNA endonuclease suitable for the HDR-directed gene and/or base editing of eukaryotic cell genomes. The genome editing efficiency of SviCas3 guided by DNA is no less than that of SviCas3 guided by RNA. In particular, t-DNA, as a template and a guide, does not require a proto-spacer-adjacent motif, demonstrating that CRISPR, as the basis for crRNA design, is not required for the SviCas3-mediated gene and base editing. This discovery will broaden our understanding of enzyme diversity in CRISPR-Cas systems, will provide important tools for the creation and modification of living things and the treatment of human genetic diseases, and will usher in a new era of DNA-guided gene editing and base editing.

Gene regulatory networks are powerful abstractions of biological systems. Since the advent of high-throughput measurement technologies in biology in the late 90s, reconstructing the structure of such networks has been a central computational problem in systems biology. While the problem is certainly not solved in its entirety, considerable progress has been made in the last two decades, with mature tools now available. This chapter aims to provide an introduction to the basic concepts underpinning network inference tools, attempting a categorisation which highlights commonalities and relative strengths. While the chapter is meant to be self-contained, the material presented should provide a useful background to the later, more specialised chapters of this book.

With the recent fast development of generative models, instruction-based image editing has shown great potential in generating high-quality images. However, the quality of editing highly depends on carefully designed instructions, placing the burden of task decomposition and sequencing entirely on the user. To achieve autonomous image editing, we present PhotoAgent, a system that advances image editing through explicit aesthetic planning. Specifically, PhotoAgent formulates autonomous image editing as a long-horizon decision-making problem. It reasons over user aesthetic intent, plans multi-step editing actions via tree search, and iteratively refines results through closed-loop execution with memory and visual feedback, without requiring step-by-step user prompts. To support reliable evaluation in real-world scenarios, we introduce UGC-Edit, an aesthetic evaluation benchmark consisting of 7,000 photos and a learned aesthetic reward model. We also construct a test set containing 1,017 photos to systematically assess autonomous photo editing performance. Extensive experiments demonstrate that PhotoAgent consistently improves both instruction adherence and visual quality compared wit

StyleGAN is arguably one of the most intriguing and well-studied generative models, demonstrating impressive performance in image generation, inversion, and manipulation. In this work, we explore the recent StyleGAN3 architecture, compare it to its predecessor, and investigate its unique advantages, as well as drawbacks. In particular, we demonstrate that while StyleGAN3 can be trained on unaligned data, one can still use aligned data for training, without hindering the ability to generate unaligned imagery. Next, our analysis of the disentanglement of the different latent spaces of StyleGAN3 indicates that the commonly used W/W+ spaces are more entangled than their StyleGAN2 counterparts, underscoring the benefits of using the StyleSpace for fine-grained editing. Considering image inversion, we observe that existing encoder-based techniques struggle when trained on unaligned data. We therefore propose an encoding scheme trained solely on aligned data, yet can still invert unaligned images. Finally, we introduce a novel video inversion and editing workflow that leverages the capabilities of a fine-tuned StyleGAN3 generator to reduce texture sticking and expand the field of view of

Large text-to-image diffusion models have achieved remarkable success in generating diverse, high-quality images. Additionally, these models have been successfully leveraged to edit input images by just changing the text prompt. But when these models are applied to videos, the main challenge is to ensure temporal consistency and coherence across frames. In this paper, we propose InFusion, a framework for zero-shot text-based video editing leveraging large pre-trained image diffusion models. Our framework specifically supports editing of multiple concepts with pixel-level control over diverse concepts mentioned in the editing prompt. Specifically, we inject the difference in features obtained with source and edit prompts from U-Net residual blocks of decoder layers. When these are combined with injected attention features, it becomes feasible to query the source contents and scale edited concepts along with the injection of unedited parts. The editing is further controlled in a fine-grained manner with mask extraction and attention fusion, which cut the edited part from the source and paste it into the denoising pipeline for the editing prompt. Our framework is a low-cost alternativ