Biology subjects

Howell, P.

Publications and source records attributed to Howell, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Centrally generated movement-related signals engage ipsilateral S1 finger representations after tetraplegia

Ipsilateral primary somatosensory cortex (S1) exhibits somatotopically organized activity during unilateral hand movements, but whether this activity depends on peripheral input remains debated. We addressed this question using functional magnetic resonance imaging (fMRI) in 14 individuals with tetraplegia and 18 able-bodied controls. Participants performed or attempted individual finger movements during 3T fMRI. We quantified movement-related univariate activity and multivariate representational structure within ipsilateral S1. Univariate activity within the anatomically defined ipsilateral S1 hand area did not differ significantly between groups, whereas a continuous spatial analysis identified greater movement-related activity in individuals with tetraplegia in S1 bands lateral to the hand representation. Multivariate analyses revealed reliable separation of finger-specific activity patterns in both groups, with no significant group difference in mean inter-finger distance. The typicality of the overall representational geometry also did not differ significantly between groups. Finally, a person with complete hand paralysis and no measurable feeling or movement still showed clear, finger-specific brain activity patterns and a typical representation of the affected hand. Together, these findings indicate that centrally generated movement-related signals can engage finger-specific representations in ipsilateral S1 without overt movement or measurable hand-related peripheral input. Ipsilateral somatotopic activity therefore cannot be explained solely by sensory reafference from the moving hand.

neuroscience↗

bioRxiv2026

Preserving Native Cellulose-Xylan Architecture Enables Structure-Property Control in Holocellulose Nanofibrils and High-Performance Sustainable Materials

The hierarchical organization of cellulose microfibrils and their intimate interactions with hemicelluloses such as xylan underpin the exceptional mechanical performance of plant cell walls. However, translating these biological design principles into sustainable nanocellulosic materials remains limited by conventional cellulose nanofibril production routes, which rely on harsh chemical treatments that disrupt the native cellulose-hemicellulose architecture. Here, we present an optimized isolation strategy for holocellulose nanofibrils (hCNFs) that preserves native cellulose structure, xylan substitution and conformation, and cellulose-xylan interactions. Using wild-type Arabidopsis thaliana, a xylan glucuronidation-deficient gux1/2 mutant, and Brassica napus straw as model systems, we systematically elucidate how xylan content and substitution pattern govern nanofibril isolation, interfacial interactions, and macroscopic properties. Two-dimensional 13C magic-angle spinning NMR demonstrates retention of native cellulose glucosyl environments, the presence of two-fold and three-fold helical xylan conformations, and cellulose-associated two-fold helical xylan. Cryogenic transmission electron microscopy reveals fibril widths of [~]3 nm, consistent with elementary cellulose I{beta} microfibrils. We show that xylan glucuronidation regulates colloidal stability, hydration behavior, and interfibrillar cohesion, whereas xylan content controls nanofibrillation efficiency. These multiscale structural features translate directly into moisture sorption, thermal behavior, and mechanical performance. Notably, Brassica napus hCNF films exhibit exceptional strength and extensibility, surpassing many chemically modified CNF systems. This work demonstrates that preserving the native cellulose-hemicellulose architecture enables high-performance, sustainable nanocellulosic materials without chemical reconstruction.

biochemistry↗

bioRxiv2026

Top-down processing alone activates the early somatosensory nuclei

The early somatosensory brainstem and thalamic nuclei are classically viewed as relays of peripheral input, yet research in animal models indicates they also receive top-down cortical signals. Whether such processing exists in humans remains unknown. Using cervical spinal cord injury (SCI), in which peripheral somatosensory input is reduced or absent while cortical processing is preserved, we tested whether top-down processing can elicit activation across the somatosensory nuclei. We combined 3 Tesla functional and quantitative MRI data to assess activity and structural properties along the somatosensory hand pathway in a cross-sectional study of 16 individuals with chronic cervical SCI (mean age {+/-} s.e.m.=52.4 {+/-} 3.5 years) and 20 age-, sex-, and handedness-matched able-bodied control subjects (mean age=50.8 {+/-} 3.5 years). Participants were visually cued to make overt or, in cases of hand paralysis, attempted right- and left-hand movements. Activation was quantified across the cuneate nucleus, ventroposterior lateral thalamus, and primary somatosensory hand cortex, while structural properties were assessed using quantitative MRI measures sensitive to myelin and tissue integrity, including magnetisation transfer saturation (MTsat) and effective transverse relaxation rate (R2*), alongside morphometric measures. Despite reduced or absent peripheral input, SCI participants exhibited robust and lateralised activation across all levels of the somatosensory pathway. This pattern persisted even in a participant with complete hand paralysis who lacked bottom-up afferent input during the fMRI task, indicating that top-down processing alone is sufficient to drive activity in early somatosensory relays. We simultaneously observed structural degeneration in the cuneate nucleus of SCI participants, marked by reduced volume and myelin-sensitive metrics (MTsat and R2*), consistent with secondary degeneration. The extent of atrophy was related to time since injury and reduced sensorimotor hand function, but showed no significant relationship with functional activation, suggesting that preserved corticocuneate signalling is not dependent on the degree of structural degeneration. This provides the first evidence that the cuneate nuclei in humans are subject to both bottom- up and top-down somatosensory processing. Although these nuclei are vulnerable to structural atrophy following dorsal column injury, our results suggest that top-down processing remains intact decades after SCI. This may have implications for the development of rehabilitation treatments targeting preserved somatosensory processing after injury.

neuroscience↗

bioRxiv2025

Differences in brain activity during sentence repetition in people who stutter: a combined analysis of four fMRI studies

Our understanding of the neural correlates of developmental stuttering benefits from the use of functional MRI (fMRI) during speech production. Despite two decades of research, however, we have reached little consensus. In the current study, we analysed pooled fMRI data from four different studies that used the same sentence reading task and methodological approach. The combined sample included 56 adolescents and adults who stutter and 53 demographically matched typically fluent controls. A sparse-sampling design was used in each study, in which participants spoke during the silent period between measurements of brain activity. Sentence reading evoked activity in both groups across frontal and temporal regions bilaterally. At statistical thresholds corrected for family-wise error, there were no significant group differences. An uncorrected threshold was applied to explore group differences in areas previously identified in earlier fMRI studies on stuttering. People who stutter (PWS) showed greater activity compared with controls in right frontal pole, right anterior insula extending to frontal operculum, left planum temporale, and midbrain, at the level of red nucleus. In contrast, PWS showed lower activity in left superior frontal sulcus, subgenual medial prefrontal cortex, right anterior temporal lobe, and portions of inferior parietal lobe bilaterally including the angular gyrus on the left. Despite pooling data across multiple studies to achieve a relatively large sample, group differences in regions involved in speech-motor control only emerged at an uncorrected voxel-wise threshold. Some of these findings align with previous fMRI studies, such as increased activity in the right anterior insular cortex.

neuroscience↗

bioRxiv2025

Revisiting face-to-hand area remapping in the human primary somatosensory cortex after a cervical spinal cord injury

Spinal cord injury (SCI) leads to profound disruptions in sensorimotor processing. Seminal research in non-human primates suggests this sensory deprivation causes functional remapping in the primary somatosensory cortex (S1), where somatotopic representations of deprived body parts, such as the hand in cervical SCI, become responsive to touch on intact body parts, such as the face. However, evidence for such remapping in humans remains inconclusive. We investigated face-to-hand remapping in 16 chronic cervical SCI patients and 21 able-bodied controls using two fMRI experiments. Experiment 1 employed a lip movement task, while Experiment 2 investigated the full architecture of S1 face reorganisation through vibrotactile stimulation of the forehead, lips and chin. We assessed (1) the level of face activity in the anatomical S1 hand area, (2) cortical shifts in peak face activity, (3) face-part separability in the S1 hand area and (4) correlations with clinical characteristics that may drive face-to-hand area remapping. Our results revealed no significant evidence in favour of face-to-hand area remapping in tetraplegic patients across markers of face-to-hand remapping during either lip movement or vibrotactile stimulation of face parts. Furthermore, our markers of remapping did not correlate with clinical characteristics. These findings suggest that cortical face-to-hand remapping is not apparent in human cervical SCI patients. Beyond providing insight into the limitations of cortical reorganisation in humans, this highlights the need to reassess rehabilitation strategies based on the assumption of large-scale face-to-hand reorganisation after an SCI.

neuroscience↗

bioRxiv2024

Distinguishing the activity of adjacent somatosensory nuclei within the brainstem using 3T fMRI

Experimental evidence in animal models indicates that the brainstem plays a major role in sensory modulation. However, mapping functional activity within the human brainstem presents many methodological challenges. These constraints have deterred essential research into human sensory brainstem processing. Here, using a 3T fMRI sequence optimised for the brainstem, combined with uni- and multivariate analysis approaches, we investigated the extent to which functional activity of neighbouring somatosensory nuclei can be delineated in the brainstem, thalamus and primary somatosensory cortex (S1). Whilst traditional univariate approaches offered limited differentiation between adjacent hand and face activation in the brainstem, multivariate classification enabled above-chance decoding of these activity patterns across S1, the thalamus, and the brainstem. Our findings establish a robust methodological approach to explore signal processing within the brainstem and across the entire somatosensory stream. This is a fundamental step towards broadening our understanding of somatosensory processing within humans and determining what changes in sensory integration may occur in clinical populations following sensory deprivation.

neuroscience↗

bioRxiv2024

TMS-based neurofeedback training of mental finger individuation induces neuroplastic changes in the sensorimotor cortex

Neurofeedback (NF) training based on motor imagery is increasingly used in neurorehabilitation with the aim to improve motor functions. However, the neuroplastic changes underpinning these improvements are poorly understood. Here, we used mental finger individuation, i.e., the selective facilitation of single finger representations without producing overt movements, as a model to study neuroplasticity induced by NF. To enhance mental finger individuation, we used transcranial magnetic stimulation (TMS)-based NF training. During motor imagery of individual finger movements, healthy participants were provided visual feedback on the size of motor evoked potentials, reflecting their finger-specific corticospinal excitability. We found that TMS-NF improved the top-down activation of finger-specific representations. First, intracortical inhibitory circuits in the primary motor cortex were tuned after training such that inhibition was selectively reduced for the finger that was mentally activated. Second, motor imagery finger representations in sensorimotor areas assessed with functional MRI became more distinct after training. Together, our results indicate that the neural underpinnings of finger individuation, a well-known model system for neuroplasticity, can be modified using TMS-NF guided motor imagery training. These findings demonstrate that TMS-NF induces neuroplasticity in the sensorimotor system, highlighting the promise of TMS-NF on the recovery of fine motor function.

neuroscience↗

bioRxiv2024

No Evidence of Altered Language Laterality in People Who Stutter across Different Brain Imaging Studies of Speech and Language

A long-standing neurobiological explanation of stuttering is the incomplete cerebral dominance theory, which refers to competition between two hemispheres for "dominance" over handedness and speech, causing altered language lateralisation. Renewed interest in these ideas came from brain imaging findings in people who stutter (PWS) of increased activity in the right hemisphere during speech production or of shifts in activity from right to left when fluency increased. Here, we revisited this theory using functional MRI data from children and adults who stutter, and typically fluent speakers (119 participants in total) during four different speech and language tasks: overt sentence reading, overt picture description, covert sentence reading and covert auditory naming. Laterality indices (LIs) were calculated for the frontal and temporal lobes using the LI toolbox running in Statistical Parametric Mapping. We also repeated the analyses with more specific language regions, namely the pars opercularis (Brodmann Area 44) and pars triangularis (Brodmann Area 45). Laterality indices in PWS and typically fluent speakers (TFS) did not differ and Bayesian analyses provided moderate to anecdotal levels of support for the null hypothesis (i.e., no differences in laterality in PWS compared with TFS). The proportions of the PWS and TFS who were left lateralised or had atypical rightwards or bilateral lateralisation did not differ. We found no support for the theory that language laterality is reduced or differs in PWS compared with TFS.

neuroscience↗

bioRxiv2023

Neuroplasticity of speech-in-noise processing in older adults assessed by functional near-infrared spectroscopy (fNIRS)

Functional near-infrared spectroscopy (fNIRS), a non-invasive optical neuroimaging technique that is portable and acoustically silent, has become a promising tool for evaluating auditory brain functions in hearing- vulnerable individuals. This study, for the first time, used fNIRS to evaluate neuroplasticity of speech-in-noise processing in older adults. Ten older adults, most of whom had moderate-to-mild hearing loss, participated in a 4-week speech-in-noise training. Their speech-in-noise performances and fNIRS brain responses to speech (auditory sentences in noise), non-speech (spectrally-rotated speech in noise) and visual (flashing chequerboards) stimuli were evaluated pre- (T0) and post-training (immediately after training, T1; and after a 4-week retention, T2). Behaviourally, speech-in-noise performances were improved after retention (T2 vs. T0) but not immediately after training (T1 vs. T0). Neurally, we intriguingly found brain responses to speech vs. non-speech decreased significantly in the left auditory cortex after retention (T2 vs. T0 and T2 vs. T1) for which we interpret as suppressed processing of background noise during speech listening alongside the significant behavioural improvements. Meanwhile, functional connectivity within and between multiple regions of temporal, parietal and frontal lobes was significantly enhanced in the speech condition after retention (T2 vs. T0). We also found neural changes before the emergence significant behavioural improvements. Compared to pre-training, responses to speech vs. non-speech in the left frontal/prefrontal cortex were decreased significantly both immediately after training (T1 vs. T0) and retention (T2 vs. T0), reflecting possible alleviation of listening efforts. Finally, connectivity was significantly decreased between auditory and higher-level non-auditory (parietal and frontal) cortices in response to visual stimuli immediately after training (T1 vs. T0), indicating decreased cross-modal takeover of speech-related regions during visual processing. The results thus showed that neuroplasticity can be observed not only at the same time, but also before behavioural changes in speech-in- noise perception. To our knowledge, this is the first fNIRS study to evaluate speech-based auditory neuroplasticity in older adults. It thus provides important implications for current research by illustrating the promises of detecting neuroplasticity using fNIRS in hearing-vulnerable individuals.

neuroscience↗

bioRxiv2022

Multi-trait ensemble genomic prediction and simulations of recurrent selection highlight importance of complex trait genetic architecture in long-term genetic gains in wheat

Cereal crop breeders have achieved considerable genetic gain in genetically complex traits, such as grain yield, while maintaining genetic diversity. However, focus on selection for yield has negatively impacted other important traits. To better understand selection within a breeding context, and how it might be optimised, we analysed genotypic and phenotypic data from a diverse, 16-founder wheat multi-parent advanced generation inter-cross (MAGIC) population. Compared to single-trait models, multi-trait ensemble genomic prediction models increased prediction accuracy for almost 90% of traits, improving grain yield prediction accuracy by 3-52%. For complex traits, non-parametric models (Random Forest) also outperformed simplified, additive models (LASSO), increasing grain yield prediction accuracy by 10-36%. Simulations of recurrent genomic selection then showed that sustained greater forward prediction accuracy optimised long-term genetic gains. Simulations of selection on grain yield found indirect responses in related traits, which involved optimisation of antagonistic trait relationships. We found multi-trait selection indices could be used to optimise undesirable relationships, such as the trade-off between grain yield and protein content, or combine traits of interest, such as yield and weed competitive ability. Simulations of phenotypic selection found that including Random Forest rather than LASSO genetic models, and multi-trait rather than single-trait models as the true genetic model, accelerated and extended long-term genetic gain whilst maintaining genetic diversity. These results suggest important roles of pleiotropy and epistasis in the wider context of wheat breeding programmes and provide insights into mechanisms for continued genetic gain in a limited genepool and optimisation of multiple traits for crop improvement.

genetics↗

bioRxiv2022

A wheat chromosome segment substitution line series supports characterisation and use of progenitor genetic variation

Genome-wide introgression and substitution lines have been developed in many plant species, enhancing mapping precision, gene discovery and the identification and exploitation of variation from wild relatives. Created over multiple generations of crossing and/or backcrossing accompanied by marker-assisted selection, the resulting introgression lines are a fixed genetic resource. In this study we report the development of spring wheat chromosome segment substitution lines generated to systematically capture genetic variation from tetraploid (Triticum turgidum ssp dicoccoides) and diploid (Aegilops tauschii) progenitor species. Generated in a common genetic background over four generations of backcrossing, the material is a base resource for the mapping and characterisation of wheat progenitor variation. To facilitate further exploitation the final population was genetically characterised using a high- density genotyping array and a range of agronomic and grain traits assessed to demonstrate the the potential use of the populations for trait localisation in wheat.

genetics↗

bioRxiv2021

Efficacy of longevity interventions in C. elegans is determined by early life activity of RNA splicing factors

Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using in vivo mini gene reporters in isogenic C. elegans, we show that alternative splicing of mRNAs related to lipid metabolism in young animals is coupled to subsequent life expectancy. Further, activity of RNA splicing factors REPO-1 and SFA-1 early in life modulates effectiveness of specific longevity interventions via POD-2/ACC1 and regulation of lipid utilization. In addition, early inhibition of REPO-1 renders animals refractory to late onset suppression of the TORC1 pathway. Together these data suggest that activity of RNA splicing factors and the metabolic landscape early in life can modulate responsiveness to longevity interventions and may explain variance in efficacy between individuals. One Sentence SummaryEfficacy of pro-longevity interventions in C. elegans is determined by the activity of splicing factors and the lipid metabolic landscape early in the life of the individual.

genetics↗

bioRxiv2020

Limited haplotype diversity underlies polygenic trait architecture across 70 years of wheat breeding

BackgroundBreeding has helped improve bread wheat yield significantly over the last century. Understanding the potential for future crop improvement depends on relating segregating genetic variation to agronomic traits. ResultsWe bred NIAB Diverse MAGIC population, comprising over 500 recombinant inbred lines, descended from sixteen bread wheat varieties released between 1935-2004. We sequenced the founders exomes and promotors by capture. Despite being highly representative of North-West European wheat and capturing 73% of global polymorphism, we found 89% of genes contained no more than three haplotypes. We sequenced each line with 0.3x coverage whole-genome sequencing, and imputed 1.1M high-quality SNPs that were over 99% concordant with array genotypes. Imputation accuracy remained high at coverage as low as 0.076x, with or without the use of founder genomes as reference panels. We created a genotype-phenotype map for 47 traits over two years. We found 136 genome-wide significant associations, concentrated at 42 genetic loci with large and often pleiotropic effects. Outside of these loci most traits are polygenic, as revealed by multi-locus shrinkage modelling. ConclusionsHistorically, wheat breeding has reshuffled a limited palette of haplotypes; continued improvement will require selection at dozens of loci of diminishing effect, as most of the major loci we mapped are known. Breeding to optimise one trait generates correlated trait changes, exemplified by the negative trade-off between yield and protein content, unless selection and recombination can break critical unfavourable trait-trait associations. Finally, low coverage whole genome sequencing of bread wheat populations is an economical and accurate genotyping strategy.

genomics↗

bioRxiv2020

Effect of Elbow Flexion Angle on Cortical Voluntary Activation of the Non-Impaired Biceps: A 3 Days Repeated Sessions Study.

Measurement of cortical voluntary activation (VA) with transcranial magnetic stimulation (TMS) is limited by technical challenges. One challenge is the difficulty in preferential stimulation of cortical neurons projecting to the target muscle and minimal stimulation of cortical neurons projecting to antagonists. Thus, the motor evoked potential (MEP) response to TMS in the target muscle compared to its primary antagonist may be an important parameter in the assessment of cortical VA. Modulating isometric elbow angle alters the magnitude of MEPs at rest. The purpose of this study was to evaluate the effect of isometric elbow flexion-extension angle on: 1) the ratio of biceps MEP relative to the triceps MEP amplitude across a range of voluntary efforts, and 2) cortical VA. Ten non-impaired participants completed three sessions wherein VA was determined using TMS at 45{degrees}, 90{degrees} and 120{degrees} of isometric elbow flexion, and peripheral electrical stimulation at 90{degrees} of elbow flexion. The biceps/triceps MEP ratio was greater in the more flexed elbow angle (120{degrees} flexion) compared to 90{degrees} during contractions of 50% and 75% of maximum voluntary contraction. Cortical VA assessed in the more extended elbow angle (45{degrees} flexion) was lower relative to 90{degrees} elbow flexion; this effect was dependent on the biceps/triceps MEP ratio. Cortical VA was sensitive to small changes in the linearity of the voluntary torque and superimposed twitch relationship, regardless of the elbow angle. Peripheral and cortical VA measures at 90{degrees} of elbow flexion were repeatable across three days. In conclusion, although the biceps/triceps MEP ratio was increased at a more flexed elbow angle relative to 90{degrees}, there was not a corresponding difference in cortical VA. Thus, increasing the MEP ratio via elbow angle did not affect estimation of cortical VA.

neuroscience↗

bioRxiv2020

Causal relationship between the right auditory cortex and speech-evoked frequency-following response: Evidence from combined tDCS and EEG

Speech-evoked envelope-following response (EFR) reflects brain encoding of speech periodicity that serves as a biomarker for pitch and speech perception and various auditory and language disorders. While EFR is thought to originate from the subcortex, recent research illustrated a right-hemispheric cortical contribution to EFR. However, it is unclear whether this contribution is causal. This study aimed to establish this causality by combining transcranial direct current stimulation (tDCS) and measurement of EFR (pre- and post-tDCS) via scalp-recorded electroencephalography (EEG). We applied tDCS over the left and right auditory cortices in right-handed normal-hearing participants and examined whether altering cortical excitability via tDCS causes changes in EFR during monaural listening to speech syllables. We showed significant changes in EFR magnitude when tDCS was applied over the right auditory cortex compared to sham stimulation for the listening ear contralateral to the stimulation site. No such effect was found when tDCS was applied over the left auditory cortex. Crucially, we further observed a hemispheric laterality where after-effect was significantly greater for tDCS applied over the right than the left auditory cortex in the contralateral ear condition. Our finding thus provides the first evidence that validates the causal relationship between the right auditory cortex and EFR.

neuroscience↗

bioRxiv2019

Relationship between neural phase-locked responses to speech and speech-in-noise perception in young and older adults

Auditory phase-locked responses are affected by aging and it has been proposed that this increases the challenges experienced during speech perception in noise (SPiN). However, this proposal lacks direct support. This issue was addressed by measuring speech-evoked phase-locked responses at subcortical (frequency-following responses, FFRs) and cortical (theta-band phase-locking, {theta}-PLV) levels, and studying the relationship between these phase-locked responses and SPiN (word report accuracies of sentences listened to in noise) in adults across a wide age-range (19-75 years old). It was found that: (1) FFR magnitudes declined with age after hearing loss was controlled for; (2) {theta}-PLV increased with age, suggesting cortical hyperexcitability in audition; (3) SPiN correlated positively with FFR magnitudes obtained in quiet and with {theta}-PLV obtained in noise, suggesting that impacts of aging (smaller FFR magnitudes and greater {theta}-PLV) on SPiN differ at subcortical and cortical levels. Thus, the current study provided evidence for different mechanisms at subcortical and cortical levels through which age affects speech-evoked phase-locked activities and SPiN.

neuroscience↗

bioRxiv2018

A chromosome-scale assembly of the major African malaria vector Anopheles funestus

BackgroundAnopheles funestus is one of the three most consequential and widespread vectors of human malaria in tropical Africa. However, the lack of a high-quality reference genome has hindered the association of phenotypic traits with their genetic basis in this important mosquito.\n\nFindingsHere we present a new high-quality An. funestus reference genome (AfunF3) assembled using 240x coverage of long-read single-molecule sequencing for contigging, combined with 100x coverage of short-read Hi-C data for chromosome scaffolding. The assembled contigs total 446 Mbp of sequence and contain substantial duplication due to alternative alleles present in the sequenced pool of mosquitos from the FUMOZ colony. Using alignment and depth-of-coverage information, these contigs were deduplicated to a 211 Mbp primary assembly, which is closer to the expected haploid genome size of 250 Mbp. This primary assembly consists of 1,053 contigs organized into 3 chromosome-scale scaffolds with an N50 contig size of 632 kbp and an N50 scaffold size of 93.811 Mbp, representing a 100-fold improvement in continuity versus the current reference assembly, AfunF1.\n\nConclusionThis highly contiguous and complete An. funestus reference genome assembly will serve as an improved basis for future studies of genomic variation and organization in this important disease vector.

bioinformatics↗

bioRxiv2018

Baseline human gut microbiota profile in healthy people and standard reporting template

A comprehensive knowledge of the types and ratios of microbes that inhabit the healthy human gut is necessary before any kind of pre-clinical or clinical study can be performed that attempts to alter the microbiome to treat a condition or improve therapy outcome. To address this need we present an innovative scalable comprehensive analysis workflow, a healthy human reference microbiome list and abundance profile (GutFeelingKB), and a novel Fecal Biome Population Report (FecalBiome) with clinical applicability. GutFeelingKB provides a list of 157 organisms (8 phyla, 18 classes, 23 orders, 38 families, 59 genera and 109 species) that forms the baseline biome and therefore can be used as healthy controls for studies related to dysbiosis. The incorporation of microbiome science into routine clinical practice necessitates a standard report for comparison of an individuals microbiome to the growing knowledgebase of \"normal\" microbiome data. The FecalBiome and the underlying technology of GutFeelingKB address this need. The knowledgebase can be useful to regulatory agencies for the assessment of fecal transplant and other microbiome products, as it contains a list of organisms from healthy individuals. In addition to the list of organisms and abundances the study also generated a list of contigs of metagenomics dark matter. In this study, metagenomic dark matter represents sequences that cannot be mapped to any known sequence but can be assembled into contigs of 10,000 nucleotides or higher. These sequences can be used to create primers to study potential novel organisms. All data is freely available from https://hive.biochemistry.gwu.edu/gfkb and NCBIs Short Read Archive.

microbiology↗