New methods to identify high peak density artifacts in Fourier transform mass spectra and to mitigate their effects on high-throughput metabolomic data analysis

Introduction

Direct injection Fourier-transform mass spectrometry (FT-MS) allows for the high-throughput and high-resolution detection of thousands of metabolite-associated isotopologues. However, spectral artifacts can generate large numbers of spectral features (peaks) that do not correspond to known compounds. Misassignment of these artifactual features creates interpretive errors and limits our ability to discern the role of representative features within living systems.

Objectives

Our goal is to develop rigorous methods that identify and handle spectral artifacts within the context of high-throughput FT-MS-based metabolomics studies.

Results

We observed three types of artifacts unique to FT-MS that we named high peak density (HPD) sites: fuzzy sites, ringing and partial ringing. While ringing artifacts are well-known, fuzzy sites and partial ringing have not been previously well-characterized in the literature. We developed new computational methods based on comparisons of peak density within a spectrum to identify regions of spectra with fuzzy sites. We used these methods to identify and eliminate fuzzy site artifacts in an example dataset of paired cancer and non-cancer lung tissue samples and evaluated the impact of these artifacts on classification accuracy and robustness.

Conclusion

Our methods robustly identified consistent fuzzy site artifacts in our FT-MS metabolomics spectral data. Without artifact identification and removal, 91.4% classification accuracy was achieved on an example lung cancer dataset; however, these classifiers rely heavily on artifactual features present in fuzzy sites. Proper removal of fuzzy site artifacts produces a more robust classifier based on non-artifactual features, with slightly improved accuracy of 92.4% in our example analysis.

     

浙江安吉上马坎遗址石制品研究

上马坎旧石器遗址发现的石制品依其总性质可归中国南方旧石器时代主工业（下简称南方主工业）。依试掘结果看,可能存在一个相对集中的活动面,在阶地顶面下311—315cm处,发现石制品13件,占试掘石标本的35.13%,占石制品的44.83%;从平面分布看,上述13件中有8件发现于513—581cm之间,由此看来活动面中心区可能偏西。该地点的时代,与宣州陈山地点对比,最早的可能不晚于距今40万年前,最晚的进入更新世晚期。     

Graphical analysis of interactions between oxidation-reduction sites in two site oxidation-reduction proteins

Many enzymes that catalyze electron-transfer reaction contain multiple oxidation-reduction centers (sites). The oxidation-reduction potential of one site as well as the kinetics of electron transfer through this site may be altered by the state of reduction of a neighboring site. Oxidation-reduction site interactions may be mechanistically important and quantitation of site interactions would aid the interpretation of thermodynamic data and possibly kinetic data. A graphical means to detect and quantitate interactions between oxidation-reduction sites from oxidation-reduction equilibrium data (type A + B in equilibrium C + D) is described and has its roots in the Scatchard analysis of ligand binding equilibria (type A + B in equilibrium C). Oxidation-reduction sites often have distinct physical properties allowing the titration behavior of specific sites to be monitored. Equilibrium measurements on specific sites of a two site protein allow a further analysis of the data which can be combined with the oxidation-reduction Scatchard analysis to solve for all four specific site equilibrium constants. Ligand binding systems can usually measure only total site binding and simplifying assumptions of identical sites or noninteracting sites are required to solve for the site specific equilibrium constants. Thus, specific site equilibrium measurements offer a distinct advantage over total site measurements. The principles of the method are illustrated by applying the graphical analysis to the two site protein, thioredoxin reductase, which contains an oxidation-reduction active site disulfide in addition to FAD. The specific site oxidation-reduction midpoint potentials (Em) of the FAD and disulfide couples of thioredoxin reductase at pH 6.0, 12 degrees C, were found to be FAD/FADH2-enzyme-(S)2 = -0.183 V, FAD/FADH2-enzyme-(SH)2 = -0.199 V, (FAD)-enzyme-(S)2/(SH)2 = -0.202 V, and (FADH2)-enzyme-(S)2/(SH)2 = -0.218 V. Hence, at pH 6.0, the FAD and disulfide sites of thioredoxin reductase have Em values that differ by approximately 0.019 V and have a negative interaction of about 0.016 V.     

丁村54：90地点石制品研究

此次研究的丁村５４：９０地点的石制品计１７１件,以大、中型为主,尤其是石器,大型者占石器总数的８３．３３％,在有刃类石器中,复刃多于单刃是其另一特点．５４：９０地点与５４：１００地点距离很近,高程相仿．两者的石制品差异显著,是有待探讨的问题．     

Salvage Archaeology at a Site Near Fort Thompson. South Dakota

Abstract

Construction of dams and reservoirs along the Missouri River has resulted in an accelerated program of archaeological field-work. Many sites have been surveyed, numerous others tested, and a lesser number extensively excavated. Surveys and test excavations will add to previously gathered data in terms of the geographical distribution of diagnostic artifacts, speculative routes of migration and cultural diffusion. The minutiae from the tested sites may offer reasons for the re-evaluation of established concepts or they may strengthen current archaeological interpretations.

The Farm School site, reported here, received limited tests. The artifact inventory suggests the presence of 2 ceramic components and contributes to information regarding the Fort Thompson and Campbell Creek foci in South Dakota.     

黄河中游晋陕峡谷陕西侧龙门至壶口段新发现的石制品

2019-2020年,在黄河中游晋陕峡谷陕西一侧龙门至壶口段新发现9处旷野旧石器地点,采集石制品136件,部分石制品直接采自地层剖面上。康家岭地点石制品的埋藏地层为马兰黄土底部的洪积碎屑层,时代可能为晚更新世早期。苏家岭地点有1件石制品出自MIS3阶段弱古土壤层之下的洪积碎屑层,光释光年龄为距今7.2±0.7万年。其余大部分石制品的埋藏地层为马兰黄土层,时代为晚更新世中、晚期,其中凉泉沟地点埋藏石制品的黄土地层光释光年龄大于距今5万年。古人类加工石制品的原料主要为砾石,岩性以石英岩为主,其次为石英,此外还有少量燧石、细砂岩和硅质岩。石制品类型包括石核、石片、石器和断块。个体大小以中小型为主。石核和石片以自然台面者为主,剥片主要采用硬锤锤击法直接剥片,少量应用砸击法。石器有中小型的刮削器、凹缺器和大型的砍砸器,均属简单石核-石片技术产品。本次新发现的旧石器地点进一步扩大了晋陕峡谷地区旧石器时代遗存的时空分布范围,有助于后续相关研究工作的开展。     

Positional artifacts in microarrays: experimental verification and construction of COP, an automated detection tool

Microarray technology is currently one of the most widely-used technologies in biology. Many studies focus on inferring the function of an unknown gene from its co-expressed genes. Here, we are able to show that there are two types of positional artifacts in microarray data introducing spurious correlations between genes. First, we find that genes that are close on the microarray chips tend to have higher correlations between their expression profiles. We call this the 'chip artifact'. Our calculations suggest that the carry-over during the printing process is one of the major sources of this type of artifact, which is later confirmed by our experiments. Based on our experiments, the measured intensity of a microarray spot contains 0.1% (for fully-hybridized spots) to 93% (for un-hybridized ones) of noise resulting from this artifact. Secondly, we, for the first time, show that genes that are close on the microtiter plates in microarray experiments also tend to have higher correlations. We call this the 'plate artifact'. Both types of artifacts exist with different severity in all cDNA microarray experiments that we analyzed. Therefore, we develop an automated web tool-COP (COrrelations by Positional artifacts) to detect these artifacts in microarray experiments. COP has been integrated with the microarray data normalization tool, ExpressYourself, which is available at http://bioinfo.mbb.yale.edu/ExpressYourself/. Together, the two can eliminate most of the common noises in microarray data.     

Filtering the surface EMG signal: Movement artifact and baseline noise contamination

The surface electromyographic (sEMG) signal that originates in the muscle is inevitably contaminated by various noise signals or artifacts that originate at the skin-electrode interface, in the electronics that amplifies the signals, and in external sources. Modern technology is substantially immune to some of these noises, but not to the baseline noise and the movement artifact noise. These noise sources have frequency spectra that contaminate the low-frequency part of the sEMG frequency spectrum. There are many factors which must be taken into consideration when determining the appropriate filter specifications to remove these artifacts; they include the muscle tested and type of contraction, the sensor configuration, and specific noise source. The band-pass determination is always a compromise between (a) reducing noise and artifact contamination, and (b) preserving the desired information from the sEMG signal. This study was designed to investigate the effects of mechanical perturbations and noise that are typically encountered during sEMG recordings in clinical and related applications. The analysis established the relationship between the attenuation rates of the movement artifact and the sEMG signal as a function of the filter band pass. When this relationship is combined with other considerations related to the informational content of the signal, the signal distortion of filters, and the kinds of artifacts evaluated in this study, a Butterworth filter with a corner frequency of 20 Hz and a slope of 12 dB/oct is recommended for general use. The results of this study are relevant to biomechanical and clinical applications where the measurements of body dynamics and kinematics may include artifact sources.     

L’industrie microlithique du Paléolithique inférieur de Bizat Ruhama, Israël

Bizat Ruhama is a lower Palaeolithic site in the southern coastal plain of Israel. The site was recently dated to ca. 1ma. In terms of lithic industry, Bizat Ruhama is a unique phenomenon amongst the Lower Palaeolithic sites in the Levant. The lithic assemblage of the site is characterized by the production of small (ca. 25mm) tools, flakes and cores. An in-depth technotypological study was made in attempt to reconstruct the production mode of these artifacts. The results presented here reveal a well-developed cognitive production process, which includes selection of special-sized raw material, production of desired blanks and their subsequent shaping into tools. The implications of this study contribute significantly to our understanding of the phenomenon of lower Palaeolithic microlithic industries in Eurasia.     

百色大梅遗址第一地点发掘简报

大梅遗址位于百色右江区东南的右江北岸,最初发现于1982年。该遗址包括三个地点,分别位于Ⅱ、Ⅲ、Ⅳ级河流阶地上。2005年8月至2006年1月,广西文物保护与考古研究所对该遗址进行抢救性考古发掘,其中第一地点(A区)发掘面积1100m~2,第二地点(包括B、C、E区)发掘面积1900m~2,第三地点(D区)发掘面1000m~2,总揭露面积4000m~2。该点出土石制品314件,包括砾石、石核、石片、石锤、石器等。石制品原料以石英岩为主,剥片和修理主要采用锤击法,工具多用砾石直接加工而成,类型有砍砸器、手镐、刮削器、尖状器等,刮削器数量最多。根据地层和出土石制品的特征推断,第一地点的时代应为旧石器时代晚期。     

Modeling the formation of Early Stone Age artifact concentrations

The nature of stone artifact concentrations at early Plio-Pleistocene sites in East Africa is evaluated with regard to hominid transport behaviors responsible for their formation. These archaeological occurrences indicate ranging behaviors involving deliberate and repeated transport of flaked stone artifacts. The stone transported to archaeological sites within the time range of Homo habilis indicates planned transport of tools or material for tool manufacture to an extent far beyond transport behaviors reported among living apes, even stone hammer-using chimpanzees. Analysis of technological evidence in a lithic assemblage at a Plio-Pleistocene site at Koobi Fora (c. 1·5 ya) indicates on-site manufacturing activities and transport of flaked stone both to and from the site locale. Possible explanations for transport of stone artifacts are discussed in view of hominid strategies of environmental exploitation and resource utilization. A model is proposed for planned, habitual transport of artifacts by hominids positively correlated with distance of planned foraging range. In this model, larger-scale sites tended to develop at locales favorably located near abundant resources, where stone imports were high but export was relaxed due to the proximity of resources to be processed.     

Influence of Artifact Removal on Rare Species Recovery in Natural Complex Communities Using High-Throughput Sequencing

Large-scale high-throughput sequencing techniques are rapidly becoming popular methods to profile complex communities and have generated deep insights into community biodiversity. However, several technical problems, especially sequencing artifacts such as nucleotide calling errors, could artificially inflate biodiversity estimates. Sequence filtering for artifact removal is a conventional method for deleting error-prone sequences from high-throughput sequencing data. As rare species represented by low-abundance sequences in datasets may be sensitive to artifact removal process, the influence of artifact removal on rare species recovery has not been well evaluated in natural complex communities. Here we employed both internal (reliable operational taxonomic units selected from communities themselves) and external (indicator species spiked into communities) references to evaluate the influence of artifact removal on rare species recovery using 454 pyrosequencing of complex plankton communities collected from both freshwater and marine habitats. Multiple analyses revealed three clear patterns: 1) rare species were eliminated during sequence filtering process at all tested filtering stringencies, 2) more rare taxa were eliminated as filtering stringencies increased, and 3) elimination of rare species intensified as biomass of a species in a community was reduced. Our results suggest that cautions be applied when processing high-throughput sequencing data, especially for rare taxa detection for conservation of species at risk and for rapid response programs targeting non-indigenous species. Establishment of both internal and external references proposed here provides a practical strategy to evaluate artifact removal process.     

Experimental Artifacts and the Analysis of Ligand Binding Data: Results of a Computer Simulation

Abstract

Use of computerized analysis techniques for ligand binding data have recently become generally available, and are now used quite routinely. When used appropriately, these tools can improve the precision of the estimated parameters for binding affinity, K, and capacity, R. Furthermore, such programs can also calculate the uncertainty of the estimates e.g., as a percent coefficient of variation (%CV). However, because of unmeasured variability in specific activity, tracer purity, counting efficiency, counter background, efficiency of separation, etc., the actual uncertainty in the parameters K and R is usually much larger than stated. In an attempt to examine the effects of such artifacts, we have developed a computer program which simulates data arising from a number of commonly used experimental designs, and then intentionally distorted with each of these artifacts. Finally, the data are converted to B/F and B and plotted in the conventional Scatchard plot. Distortions revealed in this graph are indicative of the effect each artifact has on the parameter estimates. The computer program is generally written to simulate the binding of 2 or more ligands to one, two or many classes of independent or cooperative specific sites as well as to nonspecific sites. Thus, the program is applicable in a wide variety of situations. Results show that low tracer purity (“bindability”) or low filtration efficiency will significantly alter the measured R value. Poorly determined specific radioactivity may significantly alter the measured K value as well. Imprecise measurement of machine background may result in the specious appearance of positive cooperativity, or of additional high or low affinity classes of binding sites. Finally, under some circumstances, it is possible to detect and correct for the presence of these artifacts.     

An approach to removing spatially uncorrelated artifacts from EEG recordings

This work deals with elimination artifacts from electroencephalograms (EEGs). Though many methods for solving the problem have been proposed, they either require direct intervention of the researcher, are based on additional measurements (electrooculogram, electrocardiogram, etc.), or cannot remove artifact activity to a sufficient extent. We proposed an automated method that uses of the fact that the electromyogram (EMG) is not correlated and the artifacts of electrode movement at adjacent derivations and is based on the representation of electrical activity in one derivation through activity in other derivations. The analysis of the proposed method using model signals and examples of real EEG recordings has demonstrated its practical effectiveness.     

考古标本微磨痕初步研究

从周口店第1地点和马鞍山遗址选取了20件燧石制品,以微磨痕的实验研究为基础,以扫描电子显微镜 (简称电镜) 为主要手段,通过对比分析,尝试了不同遗址间考古标本的微磨痕分析。结果表明,周口店第1地点和马鞍山遗址的石制品的功能都具有多样性;“楔” 的功能见于马鞍山遗址,并为周口店第1地点 “使用石片较多” 的说法提供了微磨痕方面的新证据。     

EEG applications for sport and performance

One approach to understanding processes that underlie skilled performing has been to study electrical brain activity using electroencephalography (EEG). A notorious problem with EEG is that genuine cerebral data is often contaminated by artifacts of non-cerebral origin. Unfortunately, such artifacts tend to be exacerbated when the subject is in motion, meaning that obtaining reliable data during exercise is inherently problematic. These problems may explain the limited number of studies using EEG as a methodological tool in the sports sciences. This paper discusses how empirical studies have generally tackled the problem of movement artifact by adopting alternative paradigms which avoid recording during actual physical exertion. Moreover, the specific challenges that motion presents to obtaining reliable EEG data are discussed along with practical and computational techniques to confront these challenges. Finally, as EEG recording in sports is often underpinned by a desire to optimise performance, a brief review of EEG-biofeedback and peak performance studies is also presented. A knowledge of practical aspects of EEG recording along with the advent of new technology and increasingly sophisticated processing models offer a promising approach to minimising, if perhaps not entirely circumventing, the problem of obtaining reliable EEG data during motion.     

百色六怀山遗址周边新发现的旧石器

六怀山遗址是百色盆地内一处重要的旧石器时代早期遗址, 2008年12月在其周边进行考查时, 新发现旧石器地点3处, 采集石制品37件。石制品类型包括石核、石片、砍砸器、手镐等; 原料主要为石英岩、石英砂岩、粉砂岩等; 石器毛坯主要为砾石, 器型粗大, 具有南方砾石石器工业的鲜明特征。初步分析显示, 新发现地点属同一时段人类活动的结果, 进一步的工作将有助于了解旷野遗址人类行为特点, 丰富中国旧石器时代考古学研究的内涵。     

山东日照黄泥梁旧石器时代遗址发掘简报

黄泥梁旧石器时代遗址埋藏于山东省日照市丝山东麓的黄土台地中,2006年发现,2011、2012年进行复查和试掘,2013年正式发掘,发掘面积约50 m2。遗址文化层厚约1.2m,位于地表下3-4m处,经光释光测定,文化层的年代为54-59 kaBP。本次发掘出土有编号的石制品1876件,包括石核、石片、石锤、工具、断块等,此外还有大量的碎屑类石制品。石料主要为脉石英和安山岩两种,大多就地取材。石制品类型以石片、断块为主,石核有一定比例,石锤上的打击痕迹明显,工具数量较少,以简单加工的刮削器为主。石制品的剥片、加工技术均为硬锤直接打击法。初步分析表明黄泥梁遗址为一处原地埋藏的石器制作场所。     

尉家小堡遗址石制品的初步研究

山西北部桑干河中游的尉家小堡遗址,是华北地区以细石器加工技术为特征的旧石器时代晚期遗址,石制品岩性以硅质岩和火山角砾岩为主。细石核全部为楔形石核,显示出一套较为成熟而稳定的制坯及剥片工艺,包括软锤修整楔状缘、压制产生细石叶等。石器类型全部为刮削器。5.6%的拼合率说明此处为原地埋藏遗址。通过与同时代桑干河流域的其他遗址石制品的比较和遗址出土较精致的穿孔骨制品的现象判断,此遗址的年代应在旧石器时代晚期之末。     

From carcass to cave: large mammal exploitation during the Aurignacian at Vogelherd, Germany

Recent results from the zooarchaeological analysis of faunal remains from Vogelherd Cave, southwestern Germany, provide new insight into the subsistence behavior of early modern human groups during the Aurignacian. The results presented here represent the first comprehensive study of the archaeofauna from this site. Several episodes of occupation are inferred at this site, taking place primarily between 31 and 32 ka. Although a wide spectrum of Pleistocene mammals is represented in the Aurignacian at Vogelherd, reindeer (Rangifer tarandus) and horse (Equus ferus) were the primary prey taxa, and they are the most appropriate data sets with which to understand human subsistence on an intrasite level. Hunting of both taxa took place during the late summer and fall, coinciding with reindeer migrations and local abundance of horses. Complete or nearly complete prey carcasses were then transported from the kill locations to the cave for processing. This study shows that Vogelherd was a preferred locale of Aurignacian groups for a broad range of activities, including the time- and labor-intensive exploitation of ungulate prey for meat, marrow, and fat resources, as well as the production and maintenance of artifacts such as figurative artwork, personal ornaments, bone and ivory armatures, and lithic tools. With its rich faunal and artifact assemblages, the Aurignacian deposit at Vogelherd provides a wealth of information on this critical period of the early Upper Paleolithic, when cultural innovations were flourishing.