Biology subjects

Bai, Y.

Publications and source records attributed to Bai, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2021

Protective effect of peroxisome proliferator-activated receptor- in regulating the early inflammation response to extended hepatectomy from a comparative transcriptomic analysis

The regulation mechanism of small-for-size syndrome remains unclear. Thus, we aimed to analyze the molecular profiles following extended hepatectomy and identify the therapeutic target. Major hepatectomy and extended hepatectomy were performed in the rat model, and the remnant livers were obtained dynamically for the high-throughput transcriptome analysis to identify the differentially expressed genes (DEGs). The general framework for weighted gene co-expression network analysis (WGCNA) was employed to explore the expression patterns of DEGs. As result, WGCNA identified 10 distinct gene co-expression modules according to the correlation between module eigengene and different postoperative time-points. The magenta module (gene count: 289) and the lightcyan module (gene count: 484) were found positively correlated with major hepatectomy instead of extended hepatectomy. In the lightcyan module, peroxisome proliferator-activated receptor- (PPAR) was selected and found the down-regulation in the remnant liver following extended (marginal) hepatectomy in rats and humans. Besides, administration of PPAR agonist attenuated hepatic inflammation injury while PPAR antagonist increased liver inflammation injury after extended hepatectomy in rats, marked by the significantly changed aminotransferases, tumor necrosis factor- and interleukin-6 levels in the plasm, and histological Suzuki criteria. Consequently, DEGs and their molecular profiles after extended hepatectomy were identified, and PPAR might be a potential therapy target for small-for-size syndrome.

genomics↗

bioRxiv2021

Robust Single-cell Matching and Multi-modalAnalysis Using Shared and Distinct FeaturesReveals Orchestrated Immune Responses

The ability to align individual cellular information from multiple experimental sources, techniques and systems is fundamental for a true systems-level understanding of biological processes. While single-cell transcriptomic studies have transformed our appreciation for the complexities and contributions of diverse cell types to disease, they can be limited in their ability to assess protein-level phenotypic information and beyond. Therefore, matching and integrating single-cell datasets which utilize robust protein measurements across multiple modalities is critical for a deeper understanding of cell states, and signaling pathways particularly within their native tissue context. Current available tools are mainly designed for single-cell transcriptomics matching and integration, and generally rely upon a large number of shared features across datasets for mutual Nearest Neighbor (mNN) matching. This approach is unsuitable when applied to single-cell proteomic datasets, due to the limited number of parameters simultaneously accessed, and lack of shared markers across these experiments. Here, we introduce a novel cell matching algorithm, Matching with pARtIal Overlap (MARIO), that takes into account both shared and distinct features, while consisting of vital filtering steps to avoid sub-optimal matching. MARIO accurately matches and integrates data from different single-cell proteomic and multi-modal methods, including spatial techniques, and has cross-species capabilities. MARIO robustly matched tissue macrophages identified from COVID-19 lung autopsies via CODEX imaging to macrophages recovered from COVID-19 bronchoalveolar lavage fluid via CITE-seq. This cross-platform integrative analysis enabled the identification of unique orchestrated immune responses within the lung of complement-expressing macrophages and their impact on the local tissue microenvironment. MARIO thus provides an analytical framework for unified analysis of single-cell data for a comprehensive understanding of the underlying biological system.

bioinformatics↗

bioRxiv2021

Sterilization of drug-resistant influenza virus through genetic interference: use of unnatural amino acid-engineered virions

The frequent emergence of drug resistance during the treatment of influenza A virus (IAV) infections highlights a need for effective antiviral countermeasures. Here, we present an antiviral method that utilizes unnatural amino acid-engineered drug-resistant (UAA-DR) virus. The engineered virus is generated through genetic code expansion to combat emerging drug-resistant viruses. The UAA-DR virus has unnatural amino acids incorporated into its drug-resistant protein and its polymerase complex for replication control. The engineered virus can undergo genomic segment reassortment with normal virus and produce sterilized progenies due to artificial amber codons in the viral genome. We validate in vitro that UAA-DR can provide a broad-spectrum antiviral strategy for several H1N1 strains, different DR-IAV strains, multidrug-resistant (MDR) strains, and even antigenically distant influenza strains (e.g., H3N2). Moreover, a minimum dose of neuraminidase (NA) inhibitors for influenza virus can further enhance the sterilizing effect when combating inhibitor-resistant strains, partly due to the promoted superinfection of unnatural amino acid-modified virus in cellular and animal models. We also exploited the engineered virus to achieve adjustable efficacy after external UAA administration, for mitigating DR virus infection on transgenic mice harboring the [Formula] pair, and to have substantial elements of the genetic code expansion technology, which further demonstrated the safety and feasibility of the strategy. We anticipate that the use of the UAA-engineered DR virion, which is a novel antiviral agent, could be extended to combat emerging drug-resistant influenza virus and other segmented RNA viruses.

bioengineering↗

bioRxiv2021

Effect of gastrointestinal alterations mimicking elderly conditions on in vitro digestion of meat and soy proteins

We evaluated the digestion of meat (chicken, beef, and pork) and soy proteins under in vitro conditions mimicking gastrointestinal (GI) conditions of adults (control, C) and elderly with achlorhydria (EA). The changes in degree of hydrolysis (DH), SDS-PAGE profiles, peptide concentration, and proteomics profiles during the digestion process were investigated. Digestion under the EA condition markedly decreased the DH of all protein sources, especially for soy protein. SDS-PAGE profiling and proteomics showed that myofibrillar/sarcoplasmic protein from meat and glycinin/beta-conglycinin from soy were the proteins most affected by the different digestive conditions. Our results indicated that the difference in the digestibility of meat protein between EA and control conditions gradually narrowed from the gastric to the intestinal phase, while a pronounced difference between control and EA conditions was maintained also in the intestinal phase. This work provides new insights of value for future dietary recommendations for elderly individuals.

biochemistry↗

bioRxiv2021

Activity-dependent circuitry plasticity via the regulation of the histamine receptor level in the Drosophila visual system

Activity-dependent synaptic plasticity is crucial for responses to the environment. Although the plasticity mechanisms of presynaptic photoreceptor neurons in the Drosophila visual system have been well studied, postsynaptic modifications remain elusive. In addition, further studies on the adaption of the visual system to different light experiences at a circuitry scale are required. Using the modified transcriptional reporter of intracellular Ca2+ method, we describe a way to visualize circuitry changes according to different light experiences. We found enhanced postsynaptic neuronal activity responses in lamina monopolar neuron L2 after prolonged light treatment. Although L1 also has connections with photoreceptors, there were no enhanced activity responses in L1. We also report in this study that activity-dependent transcriptional downregulation of inhibitory histamine receptors (HRs) occurs in postsynaptic neuron L2, but not in L1, during continuous light conditions. We expressed exogenous HR proteins in L2 neurons and found that it attenuated the enhanced activity response caused by constant light exposure. These findings, together with the fact that histamine is the main inhibitory neurotransmitter released by photoreceptors in the Drosophila visual system, confirmed our hypothesis that the activity-dependent transcriptional downregulation of HRs is responsible for the constant light exposure-induced circuitry response changes in L2. The results successfully demonstrated the selective circuit change after synaptic remodeling evoked by long-term activation and provided in vivo evidence of circuitry plasticity upon long-term environmental stimulation.

neuroscience↗

bioRxiv2021

Spatially-resolved transcriptomics analyses of invasive fronts in solid tumors

Solid tumors are complex ecosystems, and heterogeneity is the major challenge for overcoming tumor relapse and metastasis. Uncovering the spatial heterogeneity of cell types and functional states in tumors is essential for developing effective treatment, especially in invasive fronts of tumor, the most active region for tumor cells infiltration and invasion. We firstly used SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq) with a nanoscale resolution to characterize the tumor microenvironment of intrahepatic cholangiocarcinoma (ICC). Enrichment of distinctive immune cells, suppressive immune microenvironment and metabolic reprogramming of tumor cells were identified in the 500{micro}m-wide zone centered bilaterally on the tumor boundary, namely invasive fronts of tumor. Furthermore, we found the damaged states of hepatocytes with overexpression of Serum Amyloid A (SAA) in invasive fronts, recruiting macrophages for facilitating further tumor invasion, and thus resulting in a worse prognosis. We also confirmed these findings in hepatocellular carcinoma and other liver metastatic cancers. Our work highlights the remarkable potential of high-resolution-spatially resolved transcriptomic approaches to provide meaningful biological insights for comprehensively dissecting the tumor ecosystem and guiding the development of novel therapeutic strategies for solid tumors.

cancer biology↗

bioRxiv2021

Treatment with IFB-088 improves neuropathy in CMT1A and CMT1B mice

Charcot Marie Tooth diseases type 1A (CMT1A), caused by duplication of Peripheral Myelin Protein 22 (PMP22) gene, and CMT1B, caused by mutations in myelin protein zero (MPZ) gene are the two most common forms of demyelinating CMT (CMT1) and no treatments are available for either. Prior studies of the MpzSer63del mouse model of CMT1B have demonstrated that protein misfolding, endoplasmic reticulum (ER) retention and activation of the unfolded protein response (UPR) contributed to the neuropathy. Heterozygous patients with an arginine to cysteine mutation in MPZ (MPZR98C) develop a severe infantile form of CMT1B which is modeled by MpzR98C/+ mice that also show ER-stress and an activated UPR. C3-PMP22 mice are considered to effectively model CMT1A. Altered proteostasis, ER-stress and activation of the UPR have been demonstrated in mice carrying Pmp22 mutations. To determine whether enabling the ER-stress/UPR and readjusting protein homeostasis would effectively treat these models of CMT1B and CMT1A we administered Sephin1/IFB-088/icerguestat, a UPR modulator which showed efficacy in the MpzS63del model of CMT1B, to heterozygous MpzR98C and C3-PMP22 mice. Mice were analyzed by behavioral, neurophysiological, morphological and biochemical measures. Both MpzR98C/+ and C3-PMP22 mice improved in motor function and neurophysiology. Myelination, as demonstrated by g-ratios and myelin thickness, improved in CMT1B and CMT1A mice and markers of UPR activation returned towards wild type values. Taken together our results demonstrate the capability of IFB-088 to treat a second mouse model of CMT1B and a mouse model of CMT1A, the most common form of CMT. Given the recent benefits of IFB-088 treatment in Amyotrophic Lateral Sclerosis and Multiple Sclerosis animal models, these data demonstrate its potential in managing UPR and ER-stress for multiple mutations in CMT1 as well as in other neurodegenerative diseases.

neuroscience↗

bioRxiv2021

pVHL regulates protein stability of TCF/LEF transcription factor family via ubiquitin-independent proteasomal degradation

The Wnt/{beta}-catenin signaling pathway plays key roles in development and adult tissue homeostasis by controlling cell proliferation and cell fate decisions. In this pathway, transcription factors TCF/LEFs are the key components to repress target gene expression by recruiting co-repressors or to activate target gene expression by recruiting {beta}-catenin when the Wnt signals are absent or present, respectively. While progress has been made in our understanding of Wnt signaling regulation, the underlying mechanism that regulates the protein stability of the TCF/LEF family is far less clear. Here, we show that von Hippel-Lindau protein (pVHL), which is the substrate recognition component in an E3 ubiquitin ligase complex, controls TCF/LEF protein stability. Unexpectedly, pVHL directly binds to TCF/LEFs and promotes their proteasomal degradation independent of E3 ubiquitin ligase activity. Knockout of vhl in zebrafish embryos leads to a reduction of dorsal habenular neurons and this effect is upstream of dorsal habenular neurons phenotype in tcf7l2-null mutants. Our study uncovers a previously unknown mechanism for the protein stability regulation of the TCF/LEF transcription factors and demonstrates that pVHL contains a 26S proteasome binding domain that drives ubiquitin-independent proteasomal degradation. These findings provide new insights into the ubiquitin-independent actions of pVHL and uncover novel mechanistical regulation of Wnt/{beta}-catenin signaling.

cell biology↗

bioRxiv2021

A bacterium-like particle vaccine displaying Zika virus prM-E induces systemic immune responses in mice

The emergence of Zika virus (ZIKV) infection, which is an unexpectedly associated with congenital defects, has prompted the development of safe and effective vaccines. The gram-positive enhancer matrix-protein anchor (GEM-PA) display system has emerged as a versatile and highly effective platform for delivering target proteins for vaccines. In this article, we developed a bacterium-like particle vaccine ZI-{Delta}-PA-GEM based on the GEM-PA system. The fusion protein ZI-{Delta}-PA, which contains the prM-E-{Delta} protein of ZIKV (with a stem-transmembrane region deletion) and the protein anchor PA3, was expressed. The fusion protein was successfully displayed on the GEM surface, forming ZI-{Delta}-PA-GEM. Moreover, when BALB/c mice were immunized intramuscularly with ZI-{Delta}-PA-GEM combined with 201 VG and poly(I:C) adjuvants, durable ZIKV-specific IgG and protective neutralizing antibody responses were induced. Potent B cell/DC activation was also be stimulated early after immunization. Remarkably, splenocyte proliferation, the secretion of multiple cytokines, T/B cell activation and central memory T cell responses were elicited. These data indicate that ZI-{Delta}-PA-GEM is a promising bacterium-like particle vaccine candidate for ZIKV. Author summaryBecause Zika virus (ZIKV) infection is considered as an example of "disease X", the development of a safe and effective ZIKV vaccine is essential. The gram-positive enhancer matrix-protein anchor (GEM-PA) display system has been used in many vaccine studies due to its advantages. In this study, prM-E-{bigtriangleup} protein of ZIKV (with a stem-transmembrane region deletion) and the protein anchor PA3 was fusion expressed, termed ZI-{bigtriangleup}-PA. Then the fusion protein ZI-{bigtriangleup}-PA could be displayed on the surface of GEM, forming ZI-{bigtriangleup}-PA-GEM. The author evaluated the immunogenicity of ZI-{bigtriangleup}-PA-GEM with the 201 VG and poly(I:C) adjuvants. The study demonstrates that ZI-{bigtriangleup}-PA-GEM induced mice to produce neutralizing antibody and specific cellular immune responses. The author believe that the bacterium-like particle vaccine ZI-{bigtriangleup}-PA-GEM has the potential to be used as the ZIKV vaccine.

microbiology↗

bioRxiv2021

Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library

SARS-CoV-2 infection is initiated with Spike glycoprotein binding to the receptor of human angiotensin converting enzyme 2 via its receptor binding domain. Blocking this interaction is considered as an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody, VHH60, directly produced from a humanized synthetic nanobody library. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein with a KD of 2.56 nM, inhibits infections of both live SARS-CoV-2 and pseudotyped viruses harboring wildtype, escape mutations and prevailing variants at nanomolar level. VHH60 also suppresses SARS-CoV-2 infection and propagation 50-fold better and protects mice from death two times longer than that of control group after live virus inoculation on mice. VHH60 therefore is a powerful synthetic nanobody with a promising profile for disease control against COVID19.

microbiology↗

bioRxiv2021

circFL-seq reveals full-length circular RNAs with rolling circular reverse transcription and nanopore sequencing

Circular RNAs (circRNAs) act through multiple mechanisms with their sequence features to fine-tune gene expression networks. Due to overlapping sequences with linear cognates, identifying internal sequences of circRNAs remains a great challenge, which hinders comprehensive understanding of circRNA functions and mechanisms. Here, based on rolling circular reverse transcription (RCRT) and nanopore sequencing, we developed circFL-seq, a full-length circRNA sequencing method, to profile circRNA at the isoform level. With a customized computational pipeline circfull to directly identify full-length sequences from rolling circular reads, we reconstructed 77,606 high-quality circRNAs from seven human cell lines and two human tissues. Benefiting from rolling circles and long-read sequencing, circFL-seq showed more than tenfold enrichment of circRNA reads and advantages for both detection and quantification at the isoform level compared to short-read RNA sequencing. The concordance of RT-qPCR and circFL-seq results for the identification of differential alternative splicing suggested wide application prospects for functional studies of internal variants in circRNAs. Moreover, the detection of cancer-related fusion circRNAs at the omics scale may further expand the application of circFL-seq. Together, the accurate identification and quantification of full-length circRNAs make circFL-seq a potential tool for large-scale screening of functional circRNAs.

molecular biology↗

bioRxiv2021

Spatial epitope barcoding reveals subclonaltumor patch behaviors

Intratumoral variability is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are unsuitable to accurately track phenotypes and subclonal evolution within tumors, especially in response to genetic manipulations. Here, we developed epitope combinatorial tags (EpicTags), which we coupled to multiplexed ion beam imaging (EpicMIBI) for in situ tracking of barcodes within tissue microenvironments. Using this platform, we dissected the spatial component of cell lineages and phenotypes in a xenograft model of small-cell lung cancer. We observed emergent properties from mixed clones leading to the preferential expansion of subclonal patches for both neuroendocrine and non-neuroendocrine cancer cell states in this model. In tumors harboring a fraction of PTEN-deficient cancer cells, we uncovered a non-autonomous increase of subclonal patch size in PTEN wildtype cancer cells. EpicMIBI can facilitate in situ interrogation of cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity.

cancer biology↗

bioRxiv2021

Virus-Dependent Immune Conditioning of Tissue Microenvironments

A thorough understanding of complex spatial host-disease interactions in situ is necessary in order to develop effective preventative measures and therapeutic strategies. Here, we developed Protein And Nucleic acid IN situ Imaging (PANINI) and coupled it with Multiplexed Ion Beam Imaging (MIBI) to sensitively and simultaneously quantify DNA, RNA, and protein levels within the microenvironments of tissue compartments. The PANINI-MIBI approach was used to measure over 30 parameters simultaneously across large sections of archival lymphoid tissues from non-human primates that were healthy or infected with simian immunodeficiency virus (SIV), a model that accurately recapitulates human immunodeficiency virus infection (HIV). This enabled multiplexed dissection of cellular phenotypes, functional markers, viral DNA integration events, and viral RNA transcripts as resulting from viral infection. The results demonstrated immune coordination from an unexpected upregulation of IL10 in B cells in response to SIV infection that correlated with macrophage M2 polarization, thus conditioning a potential immunosuppressive environment that allows for viral production. This multiplexed imaging strategy also allowed characterization of the coordinated microenvironment around latently or actively infected cells to provide mechanistic insights into the process of viral latency. The spatial multi-modal framework presented here is applicable to deciphering tissue responses in other infectious diseases and tumor biology.

immunology↗

bioRxiv2021

AutoVEM2: a flexible automated tool to analyze candidate key mutations and epidemic trends for virus

In our previous work, we developed an automated tool, AutoVEM, for real-time monitoring the candidate key mutations and epidemic trends of SARS-CoV-2. In this research, we further developed AutoVEM into AutoVEM2. AutoVEM2 is composed of three modules, including call module, analysis module, and plot module, which can be used modularly or as a whole for any virus, as long as the corresponding reference genome is provided. Therefore, its much more flexible than AutoVEM. Here, we analyzed three existing viruses by AutoVEM2, including SARS-CoV-2, HBV and HPV-16, to show the functions, effectiveness and flexibility of AutoVEM2. We found that the N501Y locus was almost completely linked to the other 16 loci in SARS-CoV-2 genomes from the UK and Europe. Among the 17 loci, 5 loci were on the S protein and all of the five mutations cause amino acid changes, which may influence the epidemic traits of SARS-CoV-2. And some candidate key mutations of HBV and HPV-16, including T350G of HPV-16 and C659T of HBV, were detected. In brief, we developed a flexible automated tool to analyze candidate key mutations and epidemic trends for any virus, which would become a standard process for virus analysis based on genome sequences in the future. HighlightsO_LIAn automatic tool to quickly analyze candidate key mutations and epidemic trends for any virus was developed. C_LIO_LIOur integrated analysis method and tool could become a standard process for virus mutation and epidemic trend analysis based on genome sequences in the future. C_LIO_LIN501Y with the other 16 highly linked mutation sites of SARS-CoV-2 in the UK and Europe were further confirmed, and some valuable mutation sites of HBV and HPV-16 were detected. C_LI

genomics↗

bioRxiv2021

Reciprocal allostery arising from a bi-enzyme assembly controls aromatic amino acid biosynthesis in Prevotella nigrescens

Modular protein assembly has been widely reported as a mechanism for constructing allosteric machinery. Recently, a distinctive allosteric system has been identified in a bi-enzyme assembly comprising a 3-deoxy-O_SCPLOWDC_SCPLOW-arabino heptulosonate-7-phosphate synthase (DAH7PS) and chorismate mutase (CM). These enzymes catalyze the first and branch point reactions of aromatic amino acid biosynthesis in the bacterium Prevotella nigrescens (PniDAH7PS), respectively. The interactions between these two distinct catalytic domains support functional inter-reliance within this bifunctional enzyme. The binding of prephenate, the product of CM-catalyzed reaction, to the CM domain is associated with a striking rearrangement of overall protein conformation that alters the interdomain interactions and allosterically inhibits the DAH7PS activity. In this study, we observed allosteric activation of CM activity in the presence of all DAH7PS substrates. Using small angle X-ray scattering (SAXS) experiments we show that changes in overall protein conformations and dynamics are associated with the presence of different DAH7PS substrates and the allosteric inhibitor prephenate. Furthermore, we have identified an extended interhelix loop located in CM domain, loopC320-F333, as a crucial segment for the interdomain structural and catalytic communications. Our results suggest that the dual function enzyme PniDAH7PS contains a reciprocal allosteric system between the two enzymatic moieties, as a result of this bidirectional interdomain communication. This arrangement allows for a complex feedback and feedforward system for control of pathway flux by connecting the initiation and branch point of aromatic amino acid biosynthesis.

biochemistry↗

bioRxiv2021

Modulation of fatty acid elongation generates sexually dimorphic hydrocarbons and female attractiveness in Blattella germanica (L.)

Insect cuticular hydrocarbons (CHCs) serve as important intersexual signaling chemicals and generally show variation between the sexes, but little is known about the generation of sexually dimorphic hydrocarbons (SDHCs) in insects. Here, we report the molecular mechanism and biological significance that underling the generation of SDHC in the German cockroach, Blattella germanica. Sexually mature females possess more C29 cuticular hydrocarbons (CHCs), especially the contact sex pheromone precursor 3,11-DimeC29. RNAi screen against fatty acid elongase gene family members and combined with heterologous expression revealed that both BgElo12 and BgElo24 were involved in HC production, but BgElo24 is of wide catalytic activities and is able to provides substrates for BgElo12, and only the female-enriched BgElo12 was responsible for sustaining female-specific HC profile. Repressing BgElo12 masculinized the female CHC profile, decreased contact sex pheromone level and consequently reduced the sexual attractiveness of female cockroaches. Moreover, the asymmetric expression of BgElo12 between the sexes is modulated by sex differentiation cascade. Specifically, male-specific BgDsx represses the transcription of BgElo12 in males, while BgTra is able to remove this effect in females. Our study reveals a novel molecular mechanism responsible for the formation of SDHCs, and also provide evidences on shaping of the SDHCs by sexual selection, as females use them to generate high levels of contact sex pheromone.

molecular biology↗

bioRxiv2021

Manipulating vector transmission reveals local processes in bacterial communities of bats

Infectious diseases result from multiple interactions among microbes and hosts, but community ecology approaches are rarely applied. Manipulation of vector populations provides a unique opportunity to test the importance of vectors in infection cycles while also observing changes in pathogen community diversity and species interactions. Yet for many vector-borne infections in wildlife, a biological vector has not been experimentally verified and few manipulative studies have been performed. Using a captive colony of fruit bats in Ghana, we observed changes in the community of Bartonella bacteria over time after the decline and subsequent reintroduction of bat flies. With reduced transmission, community changes were attributed to ecological drift and potential selection through interspecies competition mediated by host immunity. This work demonstrated that forces maintaining diversity in communities of free-living macroorganisms act in similar ways in communities of symbiotic microorganisms, both within and among hosts. Additionally, this study is the first to experimentally test the role of bat flies as vectors of Bartonella species.

ecology↗

bioRxiv2021

Spatial modulation of individual behaviors enables collective decision-making during bacterial group migration

Coordination of individuals with diversity often requires sophisticated communications and high-order computational abilities. Microbial populations can exhibit diverse individualistic behaviors and yet can engage in collective migratory patterns with a spatially sorted arrangement of phenotypes following a self-generated attractant gradient. However, its unclear how individual bacteria without complex computational abilities can achieve the consistent group performance and determine their positions in the group while facing spatiotemporally dynamic stimuli. Here, we investigate the statistics of bacterial run-and-tumble trajectories during group migration. We discover that, despite of the constant migrating speed as a group, the individual drift velocity exhibits a spatially dependent structure that decreases from the back to the front of the group. The spatial modulation of individual stochastic behaviors constrains cells in the group, ensuring the coherent population movement with ordered patterns of phenotypes. These results reveal a simple computational principle for emergent collective behaviors from heterogeneous individuals.

microbiology↗