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PubMed2026

MACS3: A Peak-calling Platform for Bulk and Single-cell Regulatory Genomics.

Since the original publication of Model-based Analysis for ChIP-Seq (MACS), the software has been widely used to identify enriched genomic regions in ChIP-seq, ATAC-seq, CUT&RUN, DNase-seq, and related regulatory genomics assays. Over the years, MACS has evolved substantially, with MACS version 3 (MACS3) now serving as the actively maintained implementation. MACS3 preserves the core MACS framework for fragment pileup, dynamic local background noise, statistical enrichment testing, and peak refinement, while adding functionality needed for contemporary bulk and single-cell workflows. It supports conventional bulk peak calling, paired-end and fragment-based file formats, modular signal processing, direct analysis of single-cell ATAC-seq fragment files, barcode-restricted pseudobulk and cluster-level peak calling, specialized ATAC-seq and variant-calling modules, as well as command-line and programmatic interfaces. MACS3 is distributed through standard software channels and supported by continuous testing across operating systems, Python versions, and CPU architectures. Here we describe the architecture, current capabilities, and recommended use of MACS3, providing an updated reference for applying the MACS framework in contemporary bulk and single-cell regulatory genomics workflows. MACS3 is open-source software available at https://github.com/macs3-project/MACS.

Bioinformatics software↗

PubMed1991

In vivo voltammetric detection of neuropeptides with micro carbon fiber biosensors: possible selective detection of somatostatin.

The electrochemical activity of catechol- and indoleamines, measured by differential pulse voltammetry (DPV) with specifically electrically pretreated carbon fiber microelectrodes, has been utilized to develop sensitive assays for amine neurotransmitters and metabolites. So far, four oxidation peaks have been recorded in vivo between -200 and +500 mV and are well identified. We now report that by increasing the potential sweep range to +950 mV, a further peak, called Peak 5, was detected at +800 mV in vivo in the striatum of anesthetized rats. Neuropeptides containing tyrosine, tryptophan and/or cysteine appear to be electrochemically active between +600 and +900 mV in vitro in a buffered solution at pH 7.4. The present study investigates the chemical nature of Peak 5 and the possible contribution of electroactive neuropeptides to this in vivo voltammetric signal. Experiments performed in vitro and in vivo with amino acids, neuropeptides, or bacitracin (a potent peptidase inhibitor) support the view that Peak 5 is peptidergic. Furthermore, peripheral administration of cysteamine and intrastriatal injection of specific somatostatin antisera both cause the eventual disappearance of Peak 5, suggesting that somatostatin (which oxidases in vitro at approx +800 mV), or a structurally related peptide, could be the principal component of striatal Peak 5.

Animals↗

PubMed1993

The separation and identification by monoclonal antibodies of dog IgG fractions.

Four fractions of IgG from normal dog serum have been successfully isolated by gel filtration followed by protein A and protein G affinity chromatography using the fast protein liquid chromatography (FPLC) system. Protein A chromatography produced three peaks: peak 1 was fallthrough material consisting of components which did not bind to protein A, peak 2 consisted of bound material eluting at pH 6, and peak 3 contained bound material eluting at pH 3.5. The three peaks were then subjected individually to protein G affinity chromatography. Peak 1 from protein A chromatography produced a fallthrough peak followed by a weakly binding component which eluted at pH 8, and was called peak w. Peak 2 from protein A chromatography bound to protein G and eluted as a single peak at pH 3.8, and was called peak x. Peak 3 from protein A chromatography emerged as two separate peaks (y and z) off the protein G column; peak y bound and eluted at pH 4.1, and peak z bound weakly to protein G and emerged as a broad band at pH 8. Peaks w, x, y and z have been named gamma w, gamma x, gamma y and gamma z, respectively, and there purified IgG fractions were used to immunize mice for the preparation of monoclonal antibodies (McAbs). To date, two sets of McAbs have been produced: one which recognizes an epitope present in both gamma w and gamma z fractions and another set of McAbs which recognizes an epitope in the gamma x and gamma y fractions.

Animals↗

PubMed1996

Communication during the recruitment phase of a multicenter trial: the recruitment hotline.

The Bypass Angioplasty Revascularization Investigation (BARI) is a randomized trial that compares the safety and efficacy of angioplasty and bypass surgery in selected patients with multivessel coronary disease. During recruitment, the Clinical Coordinating Center (CC) required an organized manner of responding to the many questions expected from the 18 clinical sites. Thus a dedicated telephone line was established to provide the clinical sites with information quickly and ensure consistent dissemination of information. In addition, the hotline functioned as a backup mechanism for patient randomization in the event of a computer failure at one of the sites. During the first 13 months of recruitment, 1332 calls were received. The average number of daily calls peaked at 7.3 with 14 calls being the highest in any one day. Calls gradually declined as the clinical sites became more familiar with the protocol, data collection forms, and computer systems. Most questions were answered by the data management staff; however a substantial number (37%) required faculty level input. For questions that could not be answered immediately, the median time for a return call was 25 min. The BARI hotline was an efficient way to provide accurate and consistent feedback to all sites and to identify areas that required protocol clarification. It allowed rapid identification of differences in protocol interpretation across sites so that these variations could be addressed. Review of specific questions by the Operations Committee resulted in decisions on how to apply the protocol to particularly difficult or exceptional cases. While the system was labor-intensive, its benefits outweighed this disadvantage. Recommended modifications to lower costs would result in a system that could be easily adapted for use in other clinical trials.

Hotlines↗

PubMed2006

Artificial selection on male longevity influences age-dependent reproductive effort in the black field cricket Teleogryllus commodus.

Although the trade-off between reproductive effort and longevity is central to both sexual selection and evolutionary theories of aging, there has been little synthesis between these fields. Here, we selected directly on adult longevity of male field crickets Teleogryllus commodus and measured the correlated responses of age-dependent male reproductive effort, female lifetime fecundity, and several other life-history traits. Male longevity responded significantly to five generations of divergent selection. Males from downward-selected lines commenced calling sooner and reached their peak calling effort at a younger age. They called more per night and, despite living less than half as long, called more overall than males selected for increased longevity. Females from the downward-selected lines lived significantly shorter lives than females from the upward-selected lines but still produced the same number of offspring. Nymph survival, development time, and body size and weight at eclosion did not show significant correlated response to selection on male longevity, despite evidence for substantial genetic variation in each of these traits. Collectively, our findings directly support the antagonistic pleiotropy model of aging and suggest an important role for sexual selection in the aging process.

Aging↗

PubMed2006

The development of a nationwide central booking service for abortion.

BACKGROUND: Central booking services have been proven to facilitate access to abortion services. This in turn should reduce morbidity and mortality. City-wide models have previously been described. A nationwide central booking service has been developed in the UK. DEVELOPMENT: A nationwide central booking service was introduced in 1993. Initially a manual booking system was used. In 1996 the appointment system was computerised. OUTPUT: More than a quarter of a million calls are now received each year. The highest demand weekday is a Monday. The volume of calls peaks at mid-morning. There is a sustained rise in calls from the second week in January through to mid-February, peaking in the fifth week of the year. More than a quarter of calls originate from mobile phones. CONCLUSIONS: The computerised central booking service has radically improved the efficiency of the organisation. Waiting times can be actively managed using data from the system.

Abortion, Legal↗

PubMed1993

Alterations to the pattern of ultrasonic calling after prenatal exposure to aluminium sulfate.

Pregnant CBA mice were exposed to aluminium sulfate at a dose of 200 mg/kg body wt injected intraperitoneally during Days 10 to 13 of gestation. We used a variety of ethological measures, which have been shown to be sensitive indicators of toxicants, to assess effects on the mother and the behavioral development of pups. Prenatal aluminium resulted in a reduction in the rate of ultrasonic calling by pups accompanied by a shift in the timing of peak calling; treated pups exhibited decreased growth and delays in neurobehavioral development. The treatment received by a pup's foster mother was also found to influence development. We recommend ultrasonic calling as a sensitive measure in studies of behavioral teratogenicity.

Abnormalities, Drug-Induced↗

PubMed1987

Chromatographic separation of two heterogeneous forms of the catalytic subunit of cyclic AMP-dependent protein kinase holoenzyme type I and type II from striated muscle of different mammalian species.

Electrophoretically homogeneous preparations of catalytic subunit (C) of cAMP-dependent protein kinase isolated according to two different procedures from holoenzyme type I and type II from rabbit and from holoenzyme type II from rat skeletal muscle and from bovine cardiac muscle can be separated on carboxymethyl cellulose or on a Mono S column (Pharmacia) by salt gradient elution into two enzymatically active peaks called A and B, which do not interconvert on rechromatography. Cochromatography of peak A fractions or of peak B fractions derived from both holoenzymes respectively yields single enzyme peaks in each case, thus indicating that both represent different entities, which were named CA and CB. The separate character of both enzyme forms is supported by the fact that CB under all conditions is degraded faster by the C-specific protease (E. Alhanaty et al. (1981) Proc. Natl. Acad. Sci. USA 78, 3492-3495) than CA, a phenomenon which is enhanced in both enzyme forms by substrate (Kemptide). The separation of both subtypes from each other is probably based on differences in isoelectric values (delta pH less than or equal to 0.5 units). The reason for the charge difference is not presently known. CA and CB do not differ significantly in their phosphate content. No differences between CA and CB have been detectable so far with respect to their migration in SDS gels, kinetic behavior regarding both substrates and cosubstrate, pH dependence, inhibition by regulatory subunits of holoenzyme type I (rabbit skeletal muscle) and of type II (bovine cardiac muscle), and inhibition by specific-heat and acid-stable inhibitor-modulator. The peptide pattern of both forms after limited proteolysis exhibits small differences.

Animals↗

PubMed1993

Separation and partial characterization of proteinases with substrate specificity for basic amino acids from human MOLT-4 T lymphocytes: identification of those inhibited by variable-loop-V3 peptides of HIV-1 (human immunodeficiency virus-1) envelope glycoprotein.

The V3 loop of the HIV (human immunodeficiency virus)-1 envelope glycoprotein gp120 likely plays a role in HIV-1 infectivity. Although the amino acid sequence of the V3 loop is hypervariable, it contains a conserved region, Gly-Pro-Gly-Arg, that shows similarity to the active-site Gly-Pro-Cys-Arg sequence of inter-alpha-trypsin and trypstatin proteinase inhibitors. The purpose of the present work was to identify proteinases recognizing substrates with basic amino acids in the P1 substrate site that are present in MOLT-4 cells, a human CD4-positive T helper lymphocyte cell line, and to characterize these enzymes in terms of substrate, pH and ionic-strength preferences, size and susceptibility to various inhibitors, including 24- and 36-amino-acid-long V3 loop peptides. Extraction of MOLT-4 cells at low ionic strength solubilized nearly all of the trypsin-like activity, which was separable into five peaks of activity by chromatography on Mono-Q: Peaks 1, 2a, 2b, 3 and 4. All showed a neutral pH optimum, and all except Peak 4 showed optimal activity at high ionic strength. Peak 1 preferred Tos-Gly-Pro-Arg, p-nitroanilide (-pNA) substrate; Peaks 2-4 preferred benzyloxycarbonyl-Val-Leu-Gly-Arg-pNA. Peak 1, a zinc-dependent enzyme with serine and histidine in the active site, exhibited an M(r) of 75,000 on Superose 12 and was poorly inhibited by V3 loop peptides. Peak 2 contained two overlapping peaks, called 2a and 2b, that exhibited properties of zinc-dependent metalloproteinases. Gel filtration of Peak 2 activities revealed a major peak of activity at 81 kDa and a shoulder centred at 240 kDa. Each was modestly inhibited by V3 loop peptides. Peak 3, a zinc-dependent proteinase, exhibited a molecular mass of 100 kDa by gel filtration and was particularly sensitive to inhibition by V3 loop peptides. Peak 4 exhibited a molecular mass of 1100 kDa by gel filtration and was not inhibited by V3 loop peptides. None of these enzymes could be classified as mast-cell tryptase, and material in MOLT-4 cells cross-reactive with anti-(human tryptase) antibodies was not detected. Whether any of the MOLT-4 proteinases described in this study play a role in HIV-1 infectivity remains to be examined.

Amino Acid Sequence↗

PubMed1983

'Peak preference' and waveform perception.

Because the perception of waveforms has been relatively neglected in vision research, one phenomenon of waveform perception, the parsing of waves into peak-shaped rather than trough-shaped segments, is examined. It is suggested that this so-called 'peak preference' is a grouping rule which can determine figure-background segregation in some circumstances. It appears to resist explanation in terms of the spatial-filtering properties of the visual system. For a complete explanation of peak preference, the ecological significance for actions that wave stimuli would normally have in the natural setting has to be considered.

Discrimination Learning↗

PubMed2002

Seasonal variations in children's calls to a help-line: implications for preventive services.

BACKGROUND: To investigate seasonal variations in telephone calls to a help-line for children, and their correlation to changes in length of day, latitude and age. METHOD: 691,787 calls to the Red Cross Help-Line in Norway for children in the three-year period 1996-1998 were included. RESULTS: Monthly frequencies of calls deviated significantly from an expected even distribution (chi2=9446.34, df=11, P<0.0001). The frequency curve for calls peaked in April and October and had its lowest level in July and December. Variation was pronounced: the mean number of daily calls varied between 436 in July and 886 in April. There was a strong and positive correlation between the number of calls and the change in length of day across the year (r(s)=0.76, N=12, P<0.01). Increasing latitude correlated positively with the range of the monthly observed/expected ratios of calls (r(s)=0.79, N=7, P<0.05). The frequency of calls was largest among children 12 to 14 years of age. Age correlated negatively with the range of monthly observed/expected ratios of calls (r=-0.94, N=12, P<0.001). LIMITATIONS: Social and cultural factors could not be explored in the design used in the present study. CONCLUSIONS: The frequency of calls from children correlates positively with change in length of day (i.e., maximal in spring and fall), and the magnitude of the seasonal variation correlates positively with latitude and negatively with age. Knowledge of seasonal variation in requests for help may have value in planning services for children.

Adolescent↗

PubMed2002

Eigenmobilities in background electrolytes for capillary zone electrophoresis. I. System eigenpeaks and resonance in systems with strong electrolytes.

A background electrolyte system for capillary zone electrophoresis which is composed of three strong univalent ionic constituents is investigated. The ion 1 is considered as a counter-ion and two ions, 2 and 3, are considered as co-ions in relation to the analyte ion 4. We investigate the linearized model of electromigration in such a system and calculate the eigenvalues of a corresponding matrix. The model is formulated in such a way that the eigenvalues of the system are certain mobilities, which we call eigenmobilites, which characterize specific features of the electtrophoretic migration. One of the eigenmobilities is the system eigenmobility u(s) causing the rise of the system peak, called here the system eigenpeak. A situation when the analyte has the same mobility as the system eigenmobility, u(4) = u(s), is analyzed in detail. We show that it leads to the resonance-the mutual jump in the concentration profile of both co-ions, 2 and 3, has a shape of the spatial derivation of the originally sampled analyte profile and, moreover, it grows linearly with time. After a sufficiently long time it can be "amplified" to any value. The resonance has then a great impact on signals of indirect detection methods, like indirect UV detection or conductivity detection. In the framework of the linearized model the relative velocity slope S(x), a measure of electromigration dispersion, is expressed as S(x) = F(u(1) + u(4))(u(2) - u(4))(u(3) - u(4))/[u(4)(u(s) - u(4))], where u(i) is the mobility of the ith ion and F is the Faraday constant. As in practice the concentration of the analyte is not infinitely small and has a certain finite value, the analyte will be at the resonance severely dispersed to a much broader spatial interval. When a specific detector is used, the signal of such an analyte can apparently be missed without any notice.

Electrolytes↗

PubMed2006

Investigating the relation between placement of Quit antismoking advertisements and number of telephone calls to Quitline: a semiparametric modelling approach.

STUDY OBJECTIVES: Quitline-an antismoking advertising and a telephone helpline service-is an effective public health intervention strategy for tobacco control. The objective of this short report is to model the relation between placement of antismoking advertisements and calls to Quitline on a given day. METHODS/DESIGN: Data on daily Quitline antismoking advertisements, television target audience rating points (TARPS), and calls to Quitline Victoria were studied for the period 1 August 2000 and 31 July 2001. The outcome-calls to Quitline-is a count and thus assumed to follow a Poisson distribution. Generalised partial linear models were used to model the logarithm of mean daily calls as a non-parametric function of time and a linear parametric function of the day of week, number of advertisements, and TARPS. MAIN RESULTS: Peak calls to Quitline Victoria occurred during Monday to Wednesday with around three times as many calls compared with Sunday. Both placement of Quitline advertisements (p<0.001) and an increase in TARPS (p<0.001) on a given day significantly increased the number of calls made to Quitline Victoria. The model adequately captured fluctuations in call volume and diagnostics showed no model inadequacy. CONCLUSIONS: In this short report the emphasis is on modelling the parametric components-day of week, placement of advertisements, and TARPS on call volume. The dynamics of the underlying time trend in call volume is captured in a non-parametric component. Future analysis of hourly data would provide additional information to assess different media buying strategies that might increase call volume.

Adult↗

PubMed1994

Melatonin, a hormone monitorable in vivo by voltammetry?

Melatonin, an indoleamine hormone synthesized in the pinealocytes, is electroactive at the surface of pre-treated carbon fibre microelectrodes (mCFE) in vitro when using differential-pulse voltammetry (DPV), at the specific oxidation potential of approximately +570 mV. In vivo DPV experiments have then been performed in melatonergic regions such as the pineal gland or the suprachiasmatic nucleus (SCH) of anaesthetized adult male rats. These experiments indicated the feasibility of simultaneous measurements of the indolaminergic peak 3, which occurred at approximately +280 mV, due mainly to the oxidation of extracellular 5-hydroxyindoleacetic acid (5HIAA), and a signal at approximately +580 mV which we called peak M. Pharmacological in vivo experiments performed in anaesthetized rats prepared for DPV analysis with the mCFE implanted into the pineal gland or the SCH indicated that intravenous or intra-cerebral injections of exogenous melatonin (5 mg kg-1 or 2 micrograms microliter-1, n = 3, respectively) were followed by a selective and significant increase of in vivo peak M. Other in vivo experiments with anaesthetized rats prepared for DPV analysis with the mCFE into the SCH showed that tryptophan [TRY, 30 mg kg-1 intravenous (i.v.), n = 3] and n-acetyl serotonin (nA-5HT, 5 mg kg-1 i.v., n = 3), both precursors of melatonin, were responsible for a transient but significant increase in the size of peak M (approximately 320% or 126% of control levels within 10 min or 20 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed2025

Chrom-Sig: de-noising 1D genomic profiles by signal processing methods.

MOTIVATION: Modern genomic research is driven by next-generation sequencing experiments such as ChIP-seq, CUT&Tag, and CUT&RUN that generate coverage files for transcription factor binding, as well as ATAC-seq that yield coverage files for chromatin accessibility. Due to the inherent technical noise present in the experimental protocols, researchers need statistically rigorous and computationally efficient methods to extract true biological signal from a mixture of signal and noise. However, existing approaches are often computationally demanding or require input or spike-in controls. RESULTS: We developed Chrom-Sig, a Python package to quickly de-noise 1D genomic coverage tracks by computing the empirical null distribution without prior assumptions or experimental controls. When tested on 19 ChIP-seq, CUT&RUN, ATAC-seq, and snATAC-seq datasets, Chrom-Sig can effectively decompose the data into signal and noise components. Notably, Chrom-Sig performs de-noising and peak calling in 1-2 h using around 20 GB of memory. The de-noised signal corroborates with biologically meaningful results: CTCF CUT&RUN data retained a high percentage of peaks overlapping CTCF binding motifs, while ATAC-seq and RNA Polymerase II data were enriched in enhancers and promoters. We envision Chrom-Sig to be a versatile and general tool for current and future genomic technologies. AVAILABILITY AND IMPLEMENTATION: Chrom-Sig is publicly available on GitHub (https://github.com/minjikimlab/chromsig) and Zenodo (doi: 10.5281/zenodo.17488772) under the MIT licence.

Genomics↗

PubMed1995

Enhanced collagen synthesis and transcription by peak E, a contaminant of L-tryptophan preparations associated with the eosinophilia myalgia syndrome epidemic.

The pathogenesis of the eosinophilia myalgia syndrome (EMS) remains unclear. Several abnormal constituents have been found in the L-tryptophan lots responsible for the illness, particularly, 1,1-ethylidenebis[L-tryptophan], also called peak E or EBT, and 3-phenylamino-alanine or peak 5. However, the role of these contaminants in the pathogenesis of EMS and in the development of fibrosis is unknown. We now report that peak E, a dimer of L-tryptophan, is a potent stimulus for human dermal fibroblast DNA and collagen synthesis. Peak E (0.1-1.0 microM) increased DNA synthesis up to four-fold (P = 0.0001) in a dose-dependent manner (r = 0.987). When added to monolayer cultures for 2 to 24 h, peak E (0.5 to 100 microM) caused a progressive, more than threefold increase in alpha 1(I) procollagen mRNA levels and collagenous protein. No increase in procollagen mRNA levels was found after the addition of another major L-tryptophan contaminant, peak 5, or with L-tryptophan itself. Transient transfection with a 2.5-kb alpha 1(I) procollagen promoter-luciferase construct showed that peak E causes a twofold upregulation of promoter activity (P = 0.022). Contraction of collagen gels, consisting of human dermal fibroblasts incorporated into a type I collagen lattice, was enhanced two-fold by exposure to peak E (P = 0.001). We conclude that a major constituent of contaminated batches of L-tryptophan, peak E, is a potent stimulus for fibroblast activation and collagen synthesis. This stimulatory action of peak E may provide a direct mechanism for the development of fibrosis in EMS.

Cells, Cultured↗

PubMed2006

Phenomenological study of the ionisation density-dependence of TLD-100 peak 5a.

Horowitz and collaborators have reported evidence on the structure of TLD-100 peak 5. A satellite peak, called 5a, has been singled out as arising from localised electron-hole recombination in a trap/luminescent centre, its emission mechanism would be geminate recombination and, therefore, its population would depend on incident radiation ionisation density. We report a phenomenological study of peak 4, 5a and 5 strengths for glow curves previously measured at UNAM for gammas, electrons and low-energy ions. The deconvolution procedure has followed strict rules to assure that the glow curve, where the presence of peak 5a is not visually noticeable, is decomposed in a consistent fashion, maintaining fixed widths and relative temperature difference between all the peaks. We find no improvement in the quality of the fit after inclusion of peak 5a. The relative contribution of peak 5a with respect to peak 5 does not seem to correlate with the radiation linear energy transfer.

Computer Simulation↗

PubMed1981

Characterization of sub-peak b4.2, middle molecule.

The Middle Molecules (MM) within the molecular weight (MW) range of vitamin B12 (1355 daltons) are assumed to be partly responsible for uremic toxicity. We have isolated a solute, b4.2, the purity of which is controlled by thin layer chromatography on silica gel. It correlates with active clinical polyneuropathy. The Stockholm group is dealing with a MM they call peak 7c. After exchange of purified solutes between the Stockholm group and us, comparative analyses demonstrate that 7c and b4.2 are different. The b4.2 solute is a glucuronide but it is impossible to obtain the aglycon moiety after enzymatic or acidic hydrolysis. Desorption chemical ionization and electron-impact ionization mass spectrometry results of b4.2 after transformation in methyl ester trimethylsilyl derivative are compatible with a b4.2 MW of 568 daltons (or 526 in native form) corresponding to a glucuronoconjugate of an aglycon with a MW 392 daltons (or 350 in native form). Moreover mass spectrometry confirms that b4.2 isolated from normal human urine and from uremic RP6 hemofiltrate fluid are identical.

Gas Chromatography-Mass Spectrometry↗